von Jens P. Dreier ; Coline L. Lemale ; Viktor Horst ; Sebastian Major ; Vasilis Kola ; Karl Schoknecht ; Michael Lothar Scheeler ; Jed A. Hartings ; Peter Vajkoczy ; Stefan Wolf ; Johannes Woitzik ; Nils Nicholas Hecht
von Jens P. Dreier ; Svetlana Lublinsky ; Viktor Horst ; Sebastian Major ; Coline L. Lemale ; Vasilis Kola ; Maren K. L. Winkler ; Eun-Jeung Kang ; Karl Schoknecht ; Nils Hecht ; Anna Maslarova ; Edgar Santos ; Johannes Platz ; Christina M. Kowoll ; Oliver Sakowitz ; Erdem Güresir ; Hartmut Vatter ; Christian Dohmen ; Stefan Wolf ; Michael Scheel ; Peter Vajkoczy ; Jed A. Hartings ; Johannes Woitzik ; Peter Martus ; Alon Friedman
Background - We determined the predictive power of semi-automated blood-brain barrier assessment and other variables collected during neurocritical care for the outcome of ‘epilepsy or late death’ following aneurysmal subarachnoid haemorrhage. - Methods - This is a secondary analysis of the prospective, non-interventional, prognostic DISCHARGE-1-cohort from six university hospitals in Germany. All patients who underwent at least one contrast-enhanced MRI during neurocritical care were included. Initial clinical scores and Modified Rankin Scale at day 14 were available. Subdural electrocorticography was scored for seizures and spreading depolarisations. Two MRIs, one post-aneurysm occlusion and another post-neuromonitoring, were semi-automatically segmented into cerebrospinal fluid spaces, normal brain tissue, and abnormal brain tissue. Normal and abnormal tissue were further classified into tissue with “intact” or “dysfunctional” blood-brain barrier. Epilepsy and late death were determined at a median of 3.7 years. - Findings - Abnormal, barrier-dysfunctional tissue as a percentage of intracranial volume on post-monitoring MRI was the only independent predictor of early death within three weeks among 130 patients. In the 121 early survivors, this variable was also the only independent predictor of ‘epilepsy or late death’. This result, obtained by a combination of imputation and the leaving-one-out method, was confirmed in two sensitivity analyses within smaller populations and with fewer missing values. - Interpretation - The study substantiates previous experimental evidence that blood-brain barrier dysfunction plays a key role in epileptogenesis after brain injuries. Contrast-enhanced MRI, a minimally invasive technique, highlighted abnormal, barrier-dysfunctional tissue as a stand-alone independent predictor, underscoring its potential as a ‘precision medicine’ tool in early diagnosis and intervention. - Funding - JPD and AF report a grant from the Era-Net Neuron EBio2 with funds from BMBF 01EW2004 and CIHR Award No. NDD 168164. JPD reports a grant from DFG DR 323/10-2 (project number: 413848220) and EU Horizon MSCA-DN 101119916—SOPRANI. AF reports grants from the Canadian Institutes of Health Research (CIHR) PJT 148896 and Israel Science Foundation (ISF) 2254/20. NH is Berlin Institute of Health Clinical Fellow, funded by Stiftung Charité.
von Maja Krech ; Amos Muench ; Daniel Teichmann ; Peter Kuzman ; Abigail Kora Suwala ; Franziska M. Ippen ; Michael Müther ; Katharina J. Weber ; Katharina Wenger-Alakmeh ; Julia Onken ; Peter Vajkoczy ; Felix Behling ; Sven-Axel May ; Georgios Ntoulias ; Joachim K. Krauss ; Oday Atallah ; Majid Esmaeilzadeh ; Wolf C. Mueller ; Frank L. Heppner ; Helena Radbruch ; Carsten Dittmayer ; Werner Stenzel ; Arend Koch ; David Capper ; David Kaul ; Werner Paulus ; Karl Plate ; Joachim P. Steinbach ; Markus Czabanka ; Rudi Beschorner ; Andreas von Deimling ; Michael Bockmayr ; Julia E. Neumann ; Sebastian Brandner ; Teresa Krieger ; Christian Hartmann ; Christian Thomas ; Leonille Schweizer
Veröffentlicht: 11. Juni 2025 ; Gesehen am 29.10.2025
DNA methylation profiling; FGFR3; Neurocytoma; Progression-free survival; Radiotherapy
Central neurocytomas (CN) are intraventricular brain tumors predominantly occurring in young adults. Although prognosis is usually favorable, tumor recurrence is common, particularly following subtotal resection (STR). Currently, the risk of progression is evaluated using atypical features and an elevated Ki67 proliferation index. However, these markers lack consistent definitions, raising the need for objective criteria. Genome-wide DNA methylation profiles were examined in 136 tumors histologically classified as CN. Clinical/histopathological characteristics were assessed in 93/90 cases, and whole-exome sequencing was conducted in 12 cases. Clinical and molecular characteristics were integrated into a survival model to predict progression-free survival (PFS). A diagnosis of CN was epigenetically confirmed in 125 of 136 cases (92%). No DNA methylation subgroups were identified, but global DNA hypomethylation emerged as a hallmark feature of CN associated with higher recurrence risk. Risk stratification based on histological features of atypia and Ki67 proliferation index was not reproducible across neuropathologists. Hypomethylation at the FGFR3 locus, accompanied by increased FGFR3 protein expression, was observed in 97% of cases. Gross total resection was associated with significantly improved PFS compared to STR, while patients undergoing STR receiving radiotherapy had a better outcome (p = 0.0001). Younger patients were identified as having a higher risk of recurrence (p = 0.026). Patient age and treatment strategy were key factors associated with survival outcomes in this cohort. These findings underscore the importance of closer follow-up for younger patients and radiotherapy for STR cases. Furthermore, FGFR3 represents a hallmark feature and potential therapeutic target, warranting further investigation.
Acta neuropathologica Berlin : Springer, 1961 149(2025), Artikel-ID 61, Seite 1-16 Online-Ressource
Online verfügbar: 13. Februar 2025 ; Gesehen am 10.09.2025
Background - In the ESCAPE-NA1 trial, treatment with nerinetide, an eicosapeptide that interferes with post-synaptic density protein 95, was associated with improved functional outcome among patients with acute ischaemic stroke due to large vessel occlusion undergoing endovascular thrombectomy without co-treatment with an intravenous thrombolytic agent. There was no benefit when intravenous thrombolytic agent co-treatment was used. We sought to confirm the clinical benefit of nerinetide in the absence of previous intravenous thrombolytic drug treatment. - Methods - In this multicentre, randomised, double-blind, placebo-controlled study, done in 77 centres in Canada (16), the USA (16), Germany (21), Italy (four), the Netherlands (three), Norway (four), Switzerland (three), Australia (eight), and Singapore (two), we enrolled patients with acute ischaemic stroke due to anterior circulation large vessel occlusion within 12 h from onset. Eligible patients were aged 18 years or older with a disabling ischaemic stroke at the time of randomisation (baseline National Institutes of Health Stroke Scale [NIHSS] score >5), who had been functioning independently in the community (Barthel Index score >90) before the stroke, had Alberta Stroke Program Early CT Score (ASPECTS) greater than 4, and who were not treated with a plasminogen activator. Patients were randomly allocated (1:1) to receive intravenous infusion of nerinetide in a single dose of 2·6 mg/kg, up to a maximum dose of 270 mg, based upon estimated or actual weight (if known) or saline placebo using a real-time, dynamic, internet-based, stratified randomised minimisation procedure. All patients underwent endovascular thrombectomy. The primary outcome was a favourable functional outcome 90 days from randomisation, defined as a modified Rankin Scale (mRS) score of 0-2. The analysis was by intention to treat and adjusted for time from stroke onset to randomisation (≤4·5 h [yes or no]), age, sex, baseline NIHSS score, occlusion location, time from qualifying imaging to randomisation, baseline ASPECTS, and region. Secondary outcomes were measures of mortality, worsening of stroke, improved functional independence, and measures of neurological disability. This trial is registered with ClinicalTrials.gov, NCT04462536. - Findings - From Dec 6, 2020, to Jan 31, 2023, 850 patients were assigned to receive nerinetide (n=454) or placebo (n=396). 206 (45%) participants in the nerinetide group and 181 (46%) participants in the placebo group achieved an mRS score of 0-2 at 90 days (odds ratio 0·97, 95% CI 0·72-1·30; p=0·82). Serious adverse events occurred equally between groups. - Interpretation - While nerinetide did not improve outcomes in patients with acute ischaemic stroke, it was not associated with excess adverse events. Further study is needed to identify the ideal timing of treatment and the sub-population of stroke patients who might benefit from treatment combined with current reperfusion therapies. - Funding - Canadian Institutes for Health Research and NoNO.
The lancet London [u.a.] : Elsevier, 1823 405(2025), 10478 vom: Feb., Seite 560-570 Online-Ressource
von Jürgen Beck ; Christian Fung ; Daniel Strbian ; Lukas Bütikofer ; Werner J. Z'Graggen ; Matthias F. Lang ; Seraina Beyeler ; Jan Gralla ; Florian Ringel ; Karl Schaller ; Nikolaus Plesnila ; Marcel Arnold ; Werner Hacke ; Peter Jüni ; Alexander David Mendelow ; Christian Stapf ; Rustam Al-Shahi Salman ; Jenny Bressan ; Stefanie Lerch ; Arsany Hakim ; Nicolas Martinez-Majander ; Anna Piippo-Karjalainen ; Peter Vajkoczy ; Stefan Wolf ; Gerrit A. Schubert ; Anke Höllig ; Michael Veldeman ; Roland Rölz ; Andreas Gruber ; Philip Rauch ; Dorothee Wachter ; Veit Rohde ; Thomas Kerz ; Eberhard Uhl ; Enea Thanasi ; Hagen B. Huttner ; Bernd Kallmünzer ; L. Jaap Kappelle ; Wolfgang Deinsberger ; Christian Roth ; Robin Lemmens ; Jan Leppert ; Jose L. Sanmillan ; Jonathan M. Coutinho ; Katharina Hackenberg ; Gernot Reimann ; Mikael Mazighi ; Claudio L. A. Bassetti ; Heinrich P. Mattle ; Andreas Raabe ; Urs Fischer ; Renán Sánchez-Porras
BACKGROUND: It is unknown whether decompressive craniectomy improves clinical outcome for people with spontaneous severe deep intracerebral haemorrhage. The SWITCH trial aimed to assess whether decompressive craniectomy plus best medical treatment in these patients improves outcome at 6 months compared to best medical treatment alone. METHODS: In this multicentre, randomised, open-label, assessor-blinded trial conducted in 42 stroke centres in Austria, Belgium, Finland, France, Germany, the Netherlands, Spain, Sweden, and Switzerland, adults (18-75 years) with a severe intracerebral haemorrhage involving the basal ganglia or thalamus were randomly assigned to receive either decompressive craniectomy plus best medical treatment or best medical treatment alone. The primary outcome was a score of 5-6 on the modified Rankin Scale (mRS) at 180 days, analysed in the intention-to-treat population. This trial is registered with ClincalTrials.gov, NCT02258919, and is completed. FINDINGS: SWITCH had to be stopped early due to lack of funding. Between Oct 6, 2014, and April 4, 2023, 201 individuals were randomly assigned and 197 gave delayed informed consent (96 decompressive craniectomy plus best medical treatment, 101 best medical treatment). 63 (32%) were women and 134 (68%) men, the median age was 61 years (IQR 51-68), and the median haematoma volume 57 mL (IQR 44-74). 42 (44%) of 95 participants assigned to decompressive craniectomy plus best medical treatment and 55 (58%) assigned to best medical treatment alone had an mRS of 5-6 at 180 days (adjusted risk ratio [aRR] 0·77, 95% CI 0·59 to 1·01, adjusted risk difference [aRD] -13%, 95% CI -26 to 0, p=0·057). In the per-protocol analysis, 36 (47%) of 77 participants in the decompressive craniectomy plus best medical treatment group and 44 (60%) of 73 in the best medical treatment alone group had an mRS of 5-6 (aRR 0·76, 95% CI 0·58 to 1·00, aRD -15%, 95% CI -28 to 0). Severe adverse events occurred in 42 (41%) of 103 participants receiving decompressive craniectomy plus best medical treatment and 41 (44%) of 94 receiving best medical treatment. INTERPRETATION: SWITCH provides weak evidence that decompressive craniectomy plus best medical treatment might be superior to best medical treatment alone in people with severe deep intracerebral haemorrhage. The results do not apply to intracerebral haemorrhage in other locations, and survival is associated with severe disability in both groups. FUNDING: Swiss National Science Foundation, Swiss Heart Foundation, Inselspital Stiftung, and Boehringer Ingelheim.
The lancet London [u.a.] : Elsevier, 1823 403(2024), 10442 vom: Juni, Seite 2395-2404 Online-Ressource
von Fiona Niedermayer ; Kathrin Wolf ; Siqi Zhang ; Marco Dallavalle ; Nikolaos Nikolaou ; Lars Schwettmann ; Peter Selsam ; Barbara Heidi Hoffmann ; Alexandra Schneider ; Annette Peters
von Wilfried Kunde ; Julia Dal Molin ; Julia Engel ; Stefan Koch ; Tanja Kollei ; Beate Ditzen ; Thomas Ehring ; Nina Heinrichs ; Andrea Kiesel ; Peter Kirsch ; Barbara Krahé ; Thorsten Meiser ; Andreas Mojzisch ; Franz Josef Neyer ; Sabina Pauen ; Katharina Scheiter ; Christiane M. Thiel ; Oliver T. Wolf
Online veröffentlicht: 10. April 2024 ; Gesehen am 10.10.2024 ; Titel in Web of Science: Report of the Psychology Review Board in the German Research Foundation (DFG)
von Julie George ; Lukas Maas ; Nima Abedpour ; Maria Cartolano ; Laura Kaiser ; Rieke Nila Fischer ; Andreas H. Scheel ; Jan-Philipp Weber ; Martin Hellmich ; Graziella Bosco ; Caroline Volz ; Christian Müller ; Ilona Dahmen ; Felix John ; Cleidson Padua Alves ; Lisa Werr ; Jens Peter Panse ; Martin Kirschner ; Walburga Engel-Riedel ; Jessica Jürgens ; Erich Stoelben ; Michael Brockmann ; Stefan Grau ; Martin Sebastian ; Jan Alexander Stratmann ; Jens Kern ; Horst-Dieter Hummel ; Balazs Hegedus ; Martin Schuler ; Till Plönes ; Clemens Aigner ; Thomas Elter ; Karin Toepelt ; Yon-Dschun Ko ; Sylke Kurz ; Christian Grohé ; Monika Serke ; Katja Anne Höpker ; Lars Gerd Hagmeyer ; Fabian Doerr ; Khosro Hekmath ; Judith Strapatsas ; Karl-Otto Kambartel ; Geothy Chakupurakal ; Annette Hülsmeyer ; Franz-Georg Bauernfeind ; Frank Griesinger ; Anne Lüers ; Wiebke Dirks ; Rainer Gerhard Wiewrodt ; Andrea Luecke ; Ernst Michael Rodermann ; Andreas Diel ; Volker Hagen ; Kai Severin ; Roland Ullrich ; Christian Reinhardt ; Alexander Quaas ; Magdalena Bogus ; Cornelius Courts ; Peter Nürnberg ; Kerstin Becker ; Viktor Achter ; Reinhard Büttner ; Jürgen Wolf ; Martin Peifer ; Roman Thomas
von Navid Farassat ; Daniel Böhringer ; Sebastian Küchlin ; Fanni E. Molnár ; Anne Schwietering ; Dorina Seger ; Martin J. Hug ; Anja-Birte Knöbel ; Sabine Schneider-Fuchs ; Gabriele Ihorst ; Bettina Kathrin Wabbels ; Christina Beisse ; Focke Ziemssen ; Frank Schüttauf ; Andrea Martina Hedergott ; Theresia Ring-Mangold ; Claudia Schuart ; Armin Wolf ; Stefanie Schmickler ; Julia Biermann ; Philipp Eberwein ; Karsten Hufendiek ; Anja Eckstein ; Gabriele Gusek-Schneider ; Michael Peter Schittkowski ; Thomas Lischka ; Wolf A. Lagrèze
Clinical trials; Medical ophthalmology; OPHTHALMOLOGY; Paediatric ophthalmology
Introduction Myopia is a major cause of degenerative eye disease and increases the risk of secondary visual impairment. Mitigating its progression therefore has great potential of clinically relevant benefit as shown by using highly diluted atropine eye drops in children of Asian origin. However, limited evidence is available regarding the efficacy and safety of low-dose atropine therapy in non-Asian populations. Hence, the Low-dose AtropIne for Myopia Control in Children (AIM) study will test the efficacy and safety of 0.02% atropine vs placebo in a German population. - Methods and analysis AIM is a national, multicentre, prospective, randomised, placebo-controlled, double-blind trial with two parallel arms. The primary objective is to assess the efficacy of atropine 0.02% eyedrops for myopia control in children of Caucasian origin. The primary outcome is the change in cycloplegic refraction after 1 year of treatment (D/year). Secondary and tertiary outcome measures comprise the change in axial length (mm/year) in children treated with 0.02% atropine compared with placebo, the myopic progression of participants treated with 0.01% compared with 0.02% atropine (D/year and mm/year), and the safety profile of both 0.02% and 0.01% atropine. Furthermore, the myopic progression 1 year after cessation of therapy with 0.02% atropine will be evaluated. Inclusion criteria are an age of 8-12 years and myopia of −1 D to −6 D with an estimated annual myopia progression of ≥0.5 D. After randomisation, patients will receive either atropine 0.02% (arm A) or placebo eye drops (arm B) in the first year of treatment. In the second year, they will continue to receive atropine 0.02% (arm A) or switch to atropine 0.01% (arm B). In the third year, they will switch to placebo (arm A) or continue with atropine 0.01% (arm B). To achieve a statistical power of 80%, the calculated sample size is 300. The trial has started in October 2021 with a planned recruitment period of 18 months. - Ethics and dissemination AIM has been approved by the Central Ethics Committee of the University Medical Center Freiburg (21-1106), local ethics committees of each participating centre and the German Federal Institute for Drugs and Medical Devices (61-3910-4044659). It complies with the Declaration of Helsinki, local laws and ICH-GCP. Results and underlying data from this trial will be disseminated through peer-reviewed publications and conference presentations. - Trial registration number NCT03865160.
BMJ open London : BMJ Publishing Group, 2011 13(2023), 4, Artikel-ID e068822, Seite 1-11 Online-Ressource
von Sonja K. Eilts ; Johanna M. Pfeil ; Broder Poschkamp ; Tim Ulrich Krohne ; Nicole Eter ; Teresa Barth ; Rainer Guthoff ; Wolf A. Lagrèze ; Milena Grundel ; Marie-Christine Bründer ; Martin Busch ; Jayashree Kalpathy-Cramer ; Michael F. Chiang ; R. V. Paul Chan ; Aaron S. Coyner ; Susan Ostmo ; Peter Campbell ; Andreas Stahl ; Stefan Schrader
