Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder affecting multiple organ systems, with a prevalence of 1:6,760-1:13,520 live births in Germany. On the molecular level, TSC is caused by heterozygous loss-of-function variants in either of the genes TSC1 or TSC2, encoding the Tuberin-Hamartin complex, which acts as a critical upstream suppressor of the mammalian target of rapamycin (mTOR), a key signaling pathway controlling cellular growth and metabolism. Despite the therapeutic success of mTOR inhibition in treating TSC-associated manifestations, studies with mTOR inhibitors in children with TSC above two years of age have failed to demonstrate beneficial effects on disease-related neuropsychological deficits. It has thus been hypothesized, that the critical time window for mTOR inhibitors may lie in early infancy, before TSC-related symptoms such as early-onset epilepsy and infantile spasms as sign of disruptive brain maturation occur. No controlled prospective clinical trials have evaluated the effect of pre-symptomatic mTOR inhibitor therapy on neuropsychological manifestations in TSC patients under two years of age.
Orphanet journal of rare diseases London : BioMed Central, 2006 20(2025), Artikel-ID 2, Seite 1-10 Online-Ressource
von Victor Schulze-Zachau ; Nikki Rommers ; Nikos Ntoulias ; Alex Brehm ; Nadja Krug ; Ioannis Tsogkas ; Matthias Anthony Mutke ; Thilo Rusche ; Amedeo Cervo ; Claudia Rollo ; Markus Alfred Möhlenbruch ; Jessica Jesser ; Kornelia Kreiser ; Katharina Althaus ; Manuel Requena ; Marc Rodrigo-Gisbert ; Tomas Dobrocky ; Bettina L. Serrallach ; Christian H. Nolte ; Christoph Paul Riegler ; Jawed Nawabi ; Errikos Maslias ; Patrik Michel ; Guillaume Saliou ; Nathan Manning ; Alexander McQuinn ; Alon Taylor ; Christoph J. Maurer ; Ansgar Berlis ; Daniel Kaiser ; Ani Cuberi ; Manuel Moreu ; Alfonso López-Frías ; Carlos Pérez-García ; Riitta Rautio ; Ylikotila Pauli ; Nicola Limbucci ; Leonardo Renieri ; Isabel Fragata ; Tania Rodriguez-Ares ; Jan Kirschke ; Julian Schwarting ; Sami Al Kasab ; Alejandro M. Spiotta ; Ahmad Abu Qdais ; Adam A. Dmytriw ; Robert W. Regenhardt ; Aman B. Patel ; Vitor Mendes Pereira ; Nicole M. Cancelliere ; Carsten Schmeel ; Franziska Dorn ; Malte Sauer ; Grzegorz Marek Karwacki ; Jane Khalife ; Ajith Thomas ; Hamza A. Shaikh ; Christian Commodaro ; Marco Pileggi ; Roland Schwab ; Flavio Bellante ; Anne Dusart ; Jeremy Hofmeister ; Paolo Machi ; Edgar A. Samaniego ; Diego J. Ojeda ; Robert M. Starke ; Ahmed Abdelsalam ; Frans van den Bergh ; Sylvie De Raedt ; Maxim Bester ; Fabian Flottmann ; Daniel Arvid Weiß ; Marius Kaschner ; Peter T. Kan ; Gautam Edhayan ; Michael R. Levitt ; Spencer L. Raub ; Mira Katan ; Urs Fischer ; Marios-Nikos Psychogios
Introduction: Thrombectomy complications remain poorly explored. This study aims to characterize periprocedural intracranial vessel perforation including the effect of thrombolysis on patient outcomes. - Patients and methods: In this multicenter retrospective cohort study, consecutive patients with vessel perforation during thrombectomy between January 2015 and April 2023 were included. Vessel perforation was defined as active extravasation on digital subtraction angiography. The primary outcome was modified Rankin Scale (mRS) at 90 days. Factors associated with the primary outcome were assessed using proportional odds models. - Results: 459 patients with vessel perforation were included (mean age 72.5 ± 13.6 years, 59% female, 41% received thrombolysis). Mortality at 90 days was 51.9% and 16.3% of patients reached mRS 0-2 at 90 days. Thrombolysis was not associated with worse outcome at 90 days. Perforation of a large vessel (LV) as opposed to medium/distal vessel perforation was independently associated with worse outcome at 90 days (aOR 1.709, p = 0.04) and LV perforation was associated with poorer survival probability (HR 1.389, p = 0.021). Patients with active bleeding >20 min had worse survival probability, too (HR 1.797, p = 0.009). Thrombolysis was not associated with longer bleeding duration. Bleeding cessation was achieved faster by permanent vessel occlusion compared to temporary measures (median difference: 4 min, p < 0.001). - Discussion and conclusion: Vessel perforation during thrombectomy is a severe and frequently fatal complication. This study does not suggest that thrombolysis significantly attributes to worse prognosis. Prompt cessation of active bleeding within 20 min is critical, emphasizing the need for interventionalists to be trained in complication management.
European stroke journal London : Sage Publishing, 2016 10(2025), 1, Seite 63-73 Online-Ressource
von Marius Kaschner ; Thorsten Lichtenstein ; Daniel Weiss ; Bernd Turowski ; Lukas Goertz ; Claudia Kluner ; Marc Schlamann ; Christian Mathys ; Christoph Kabbasch
von Sven Dittrich ; Joseph George Pattathu ; Friedrich Ebinger ; Joachim Eichhorn ; Reinald Motz ; Christoph Korenke ; Matthias Freund ; Michael Schumacher
X-linked Duchenne muscular dystrophy (DMD), the most frequent human hereditary skeletal muscle myopathy, inevitably leads to progressive dilated cardiomyopathy. We assessed the effect and safety of a combined treatment with the ACE-inhibitor enalapril and the β-blocker metoprolol in a German cohort of infantile and juvenile DMD patients with preserved left ventricular function.
Orphanet journal of rare diseases London : BioMed Central, 2006 14(2019), Artikel-ID 105, Seite 1-13 Online-Ressource
von Frank Bloos ; Daniel Thomas-Rüddel ; Hendrik Rüddel ; Christoph Engel ; Daniel Schwarzkopf ; John C. Marshall ; Stephan Harbarth ; Philipp Simon ; Reimer Riessen ; Didier Keh ; Karin Dey ; Manfred Weiß ; Susanne Toussant ; Dirk Schädler ; Andreas Weyland ; MAximilian Ragaller ; Konrad Schwarzkopf ; Jürgen Eiche ; Gerhard Kuhnle ; Heike Hoyer ; Christiane Hartog ; Udo Kaisers ; Konrad Reinhard
