TY - JOUR A1 - Traub, Jan A1 - Otto, Markus A1 - Sell, Roxane A1 - Göpfert, Dennis A1 - Homola, György A1 - Steinacker, Petra A1 - Oeckl, Patrick A1 - Morbach, Caroline A1 - Frantz, Stefan A1 - Pham, Mirko A1 - Störk, Stefan A1 - Stoll, Guido A1 - Frey, Anna T1 - Serum phosphorylated tau protein 181 and neurofilament light chain in cognitively impaired heart failure patients JF - Alzheimer's Research & Therapy N2 - Background Chronic heart failure (HF) is known to increase the risk of developing Alzheimer’s dementia significantly. Thus, detecting and preventing mild cognitive impairment, which is common in patients with HF, is of great importance. Serum biomarkers are increasingly used in neurological disorders for diagnostics, monitoring, and prognostication of disease course. It remains unclear if neuronal biomarkers may help detect cognitive impairment in this high-risk population. Also, the influence of chronic HF and concomitant renal dysfunction on these biomarkers is not well understood. Methods Within the monocentric Cognition.Matters-HF study, we quantified the serum levels of phosphorylated tau protein 181 (pTau) and neurofilament light chain (NfL) of 146 extensively phenotyped chronic heart failure patients (aged 32 to 85 years; 15.1% women) using ultrasensitive bead-based single-molecule immunoassays. The clinical work-up included advanced cognitive testing and cerebral magnetic resonance imaging (MRI). Results Serum concentrations of NfL ranged from 5.4 to 215.0 pg/ml (median 26.4 pg/ml) and of pTau from 0.51 to 9.22 pg/ml (median 1.57 pg/ml). We detected mild cognitive impairment (i.e., T-score < 40 in at least one cognitive domain) in 60% of heart failure patients. pTau (p = 0.014), but not NfL, was elevated in this group. Both NfL (ρ = − 0.21; p = 0.013) and pTau (ρ = − 0.25; p = 0.002) related to the cognitive domain visual/verbal memory, as well as white matter hyperintensity volume and cerebral and hippocampal atrophy. In multivariable analysis, both biomarkers were independently influenced by age (T = 4.6 for pTau; T = 5.9 for NfL) and glomerular filtration rate (T = − 2.4 for pTau; T = − 3.4 for NfL). Markers of chronic heart failure, left atrial volume index (T = 4.6) and NT-proBNP (T = 2.8), were further cardiological determinants of pTau and NfL, respectively. In addition, pTau was also strongly affected by serum creatine kinase levels (T = 6.5) and ferritin (T = − 3.1). Conclusions pTau and NfL serum levels are strongly influenced by age-dependent renal and cardiac dysfunction. These findings point towards the need for longitudinal examinations and consideration of frequent comorbidities when using neuronal serum biomarkers. KW - Alzheimer’s dementia KW - heart failure KW - cognitive impairment KW - neurofilament light chain KW - phosphorylated tau protein KW - renal function KW - age Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300515 VL - 14 ER - TY - JOUR A1 - Herrmann, David P. A1 - Müller-Graff, Franz-Tassilo A1 - Kaulitz, Stefan A1 - Cebulla, Mario A1 - Kurz, Anja A1 - Hagen, Rudolf A1 - Neun, Tilmann A1 - Rak, Kristen T1 - Application of intentional facial nerve stimulation during cochlear implantation as an electrophysiological tool to estimate the intracochlear electrode position JF - Scientific Reports N2 - This proof of concept describes the use of evoked electromyographic (EMG) activation of the facial nerve for intraoperative monitoring of the electrode insertion during cochlear implantation (CI). Intraoperative EMG measurements from the facial nerve were conducted in nine patients undergoing CI implantation. Electric current pulses were emitted from contacts on the CI array during and immediately after electrode insertion. For control, the results of EMG measurements were compared to postoperative flat panel volume computed tomography scans with secondary reconstruction (fpVCT\(_{SECO}\)). During insertion, the EMG response evoked by the electrical stimulation from the CI was growing with the stimulating contact approaching the facial nerve and declined with increasing distance. After full insertion, contacts on the apical half of the CI array stimulated higher EMG responses compared with those on the basal half. Comparison with postoperative imaging demonstrated that electrode contacts stimulating high EMG responses had the shortest distances to the facial nerve. It could be demonstrated that electrically evoked EMG activation of the facial nerve can be used to monitor the progress during CI electrode insertion and to control the intracochlear electrode position after full insertion. KW - facial nerve KW - electromyographic KW - cochlear implantation Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300197 VL - 12 IS - 1 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 - 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 - Merkel, Helena A1 - Lindner, Dirk A1 - Gaber, Khaled A1 - Ziganshyna, Svitlana A1 - Jentzsch, Jennifer A1 - Mucha, Simone A1 - Gerhards, Thilo A1 - Sari, Sabine A1 - Stock, Annika A1 - Vothel, Felicitas A1 - Falter, Lea A1 - Quäschling, Ulf A1 - Hoffmann, Karl-Titus A1 - Meixensberger, Jürgen A1 - Halama, Dirk A1 - Richter, Cindy T1 - Standardized classification of cerebral vasospasm after subarachnoid hemorrhage by digital subtraction angiography JF - Journal of Clinical Medicine N2 - Background: During the last decade, cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) was a current research focus without a standardized classification in digital subtraction angiography (DSA). This study was performed to investigate a device-independent visual cerebral vasospasm classification for endovascular treatment. Methods: The analyses are DSA based rather than multimodal. Ten defined points of intracranial arteries were measured in 45 patients suffering from cerebral vasospasm after SAH at three time points (hospitalization, before spasmolysis, control after six months). Mathematical clustering of vessel diameters was performed to generate four objective grades for comparison. Six interventional neuroradiologists in two groups scored 237 DSAs after a new visual classification (grade 0–3) developed on a segmental pattern of vessel contraction. For the second group, a threshold-based criterion was amended. Results: The raters had a reproducibility of 68.4% in the first group and 75.2% in the second group. The complementary threshold-based criterion increased the reproducibility by about 6.8%, while the rating deviated more from the mathematical clustering in all grades. Conclusions: The proposed visual classification scheme of cerebral vasospasm is suitable as a standard grading procedure for endovascular treatment. There is no advantage of a threshold-based criterion that compensates for the effort involved. Automated vessel analysis is superior to compare inter-group results in research settings. KW - cerebral vasospasm KW - subarachnoid hemorrhage KW - classification KW - vessel diameter Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-270638 SN - 2077-0383 VL - 11 IS - 7 ER - TY - JOUR A1 - Gaab, Christine A1 - Adolph, Jonas E. A1 - Tippelt, Stephan A1 - Mikasch, Ruth A1 - Obrecht, Denise A1 - Mynarek, Martin A1 - Rutkowski, Stefan A1 - Pfister, Stefan M. 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 - Sträter, Ronald A1 - Bode, Udo A1 - Faldum, Andreas A1 - Kwiecien, Robert A1 - Fleischhack, Gudrun T1 - Local and systemic therapy of recurrent medulloblastomas in children and adolescents: results of the P-HIT-REZ 2005 Study JF - Cancers N2 - Recurrent medulloblastomas are associated with survival rates <10%. Adequate multimodal therapy is being discussed as having a major impact on survival. In this study, 93 patients with recurrent medulloblastoma treated in the German P-HIT-REZ 2005 Study were analyzed for survival (PFS, OS) dependent on patient, disease, and treatment characteristics. The median age at the first recurrence was 10.1 years (IQR: 6.9–16.1). Median PFS and OS, at first recurrence, were 7.9 months (CI: 5.7–10.0) and 18.5 months (CI: 13.6–23.5), respectively. Early relapses/progressions (<18 months, n = 30/93) found mainly in molecular subgroup 3 were associated with markedly worse median PFS (HR: 2.34) and OS (HR: 3.26) in regression analyses. A significant survival advantage was found for the use of volume-reducing surgery as well as radiotherapy. Intravenous chemotherapy with carboplatin and etoposide (ivCHT, n = 28/93) showed improved PFS and OS data and the best objective response rate (ORR) was 66.7% compared to oral temozolomide (oCHT, n = 47/93) which was 34.8%. Intraventricular (n = 43) as well as high-dose chemotherapy (n = 17) at first relapse was not related to a significant survival benefit. Although the results are limited due to a non-randomized study design, they may serve as a basis for future treatment decisions in order to improve the patients' survival. KW - medulloblastoma KW - refractory KW - recurrent KW - children KW - chemotherapy KW - surgery KW - radiotherapy KW - re-irradiation KW - intraventricular therapy Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-254809 SN - 2072-6694 VL - 14 IS - 3 ER - TY - JOUR A1 - Traub, Jan A1 - Otto, Markus A1 - Sell, Roxane A1 - Homola, György A. A1 - Steinacker, Petra A1 - Oeckl, Patrick A1 - Morbach, Caroline A1 - Frantz, Stefan A1 - Pham, Mirko A1 - Störk, Stefan A1 - Stoll, Guido A1 - Frey, Anna T1 - Serum glial fibrillary acidic protein indicates memory impairment in patients with chronic heart failure JF - ESC Heart Failure N2 - Aims Cognitive dysfunction occurs frequently in patients with heart failure (HF), but early detection remains challenging. Serum glial fibrillary acidic protein (GFAP) is an emerging biomarker of cognitive decline in disorders of primary neurodegeneration such as Alzheimer's disease. We evaluated the utility of serum GFAP as a biomarker for cognitive dysfunction and structural brain damage in patients with stable chronic HF. Methods and results Using bead-based single molecule immunoassays, we quantified serum levels of GFAP in patients with HF participating in the prospective Cognition.Matters-HF study. Participants were extensively phenotyped, including cognitive testing of five separate domains and magnetic resonance imaging (MRI) of the brain. Univariable and multivariable models, also accounting for multiple testing, were run. One hundred and forty-six chronic HF patients with a mean age of 63.8 ± 10.8 years were included (15.1% women). Serum GFAP levels (median 246 pg/mL, quartiles 165, 384 pg/mL; range 66 to 1512 pg/mL) did not differ between sexes. In the multivariable adjusted model, independent predictors of GFAP levels were age (T = 5.5; P < 0.001), smoking (T = 3.2; P = 0.002), estimated glomerular filtration rate (T = −4.7; P < 0.001), alanine aminotransferase (T = −2.1; P = 0.036), and the left atrial end-systolic volume index (T = 3.4; P = 0.004). NT-proBNP but not serum GFAP explained global cerebral atrophy beyond ageing. However, serum GFAP levels were associated with the cognitive domain visual/verbal memory (T = −3.0; P = 0.003) along with focal hippocampal atrophy (T = 2.3; P = 0.025). Conclusions Serum GFAP levels are affected by age, smoking, and surrogates of the severity of HF. The association of GFAP with memory dysfunction suggests that astroglial pathologies, which evade detection by conventional MRI, may contribute to memory loss beyond ageing in patients with chronic HF. KW - Glial fibrillary acidic protein KW - GFAP KW - Chronic heart failure KW - Cognitive decline KW - Memory dysfunction KW - Brain atrophy Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-312736 VL - 9 IS - 4 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 -