Review
Biochemistry & Molecular Biology
Ekaterina Bychkova, Marina Dorofeeva, Aleksandr Levov, Alexey Kislyakov, Kristina Karandasheva, Vladimir Strelnikov, Kirill Anoshkin
Summary: Patients with tuberous sclerosis complex display cognitive, behavioral, and psychiatric impairments linked to cortical tubers. These tubers are caused by mutations in TSC1 or TSC2 genes, resulting in overactivation of the mTOR pathway. However, the formation of cortical tubers may involve more complex molecular mechanisms that require further investigation.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2023)
Article
Immunology
Xian-Hui Huang, Yao Ma, Han Lou, Na Chen, Ting Zhang, Liu-Ying Wu, Yi-Ju Chen, Meng-Meng Zheng, Yong-Liang Lou, Dan-Li Xie
Summary: The TSC1-mTOR signaling pathway plays a crucial role in regulating the innate immunity against V. vulnificus infection, with TSC1 deficiency leading to enhanced M1 response and impaired bactericidal activity in macrophages. Inhibition of mTOR activity can reverse the hypersensitive M1 response induced by V. vulnificus infection.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Clinical Neurology
Roland Coras, Hans Holthausen, Harvey B. Sarnat
Summary: The ILAE classification of Focal Cortical Dysplasia (FCD) from 2011 has been widely accepted and used, particularly focusing on three subtypes where FCD Type 2 has been validated extensively compared to Type 1 and Type 3. Further research is needed to provide comprehensive clinico-pathological specifications for FCD Type 1B and 1C as well as to establish a valid animal model for FCD Type 1.
Article
Clinical Neurology
Victoria-Elisabeth Gruber, Mark J. Luinenburg, Katrin Colleselli, Verena Endmayr, Jasper J. Anink, Till S. Zimmer, Floor Jansen, Peter Gosselaar, Roland Coras, Theresa Scholl, Ingmar Blumcke, Jose Pimentel, Johannes A. Hainfellner, Romana Hoeftberger, Karl Roessler, Martha Feucht, Jackelien Scheppingen, Eleonora Aronica, Angelika Muehlebner
Summary: This study found that C3 protein expression was significantly upregulated in white and gray matter lesions of TSC and FCD2B, while synaptophysin showed a remarkable increase in the white matter of both diseases. Confocal imaging revealed colocalization of complement factors with various cell types, suggesting that complement pathway overactivation may play a role in the pathogenesis of TSC and FCD2B.
Article
Clinical Neurology
Amanda Almacellas Barbanoj, Robert T. Graham, Benito Maffei, Jenna C. Carpenter, Marco Leite, Justin Hoke, Felisia Hardjo, James Scott-Solache, Christos Chimonides, Stephanie Schorge, Dimitri M. Kullmann, Vincent Magloire, Gabriele Lignani
Summary: Focal cortical dysplasias are a common type of cortical development abnormality that often leads to cognitive and behavioral abnormalities as well as drug-resistant epilepsy. A gene therapy approach targeting the overexpression of the Kv1.1 potassium channel has shown promising results in reducing seizures in a mouse model of frontal lobe focal cortical dysplasia.
Article
Genetics & Heredity
Hirofumi Kashii, Shinya Kasai, Atsushi Sato, Yoko Hagino, Yasumasa Nishito, Toshiyuki Kobayashi, Okio Hino, Masashi Mizuguchi, Kazutaka Ikeda
Summary: The study found that double mutations in the TSC1 and TSC2 genes lead to the occurrence of autism spectrum disorder, similar to TSC2 mutations. The double mutations cause significant changes in gene expression and contribute to the genotype-phenotype correlations in TSC.
Article
Clinical Neurology
Till S. Zimmer, Anatoly Korotkov, Susan Zwakenberg, Floor E. Jansen, Fried J. T. Zwartkruis, Nicholas R. Rensing, Michael Wong, Angelika Muhlebner, Erwin A. van Vliet, Eleonora Aronica, James D. Mills
Summary: This study identified a novel transcription factor, SPI1/PU.1, which is involved in the pro-inflammatory gene expression in malformed cells in TSC and FCD 2b. The expression of SPI1/PU.1 is associated with mTOR activation, oxidative stress, and seizure development, providing potential therapeutic targets for genetic epilepsies.
Article
Medicine, Research & Experimental
Kakeru Hosomoto, Tatsuya Sasaki, Koji Kawai, Yosuke Okazaki, Yuki Hyodo, Takashi Shibata, Susumu Sasada, Takao Yasuhara, Katsuhiro Kobayashi, Hiroyuki Yanai, Isao Date
Summary: We report a case of refractory epilepsy caused by a solitary cortical tuber mimicking focal cortical dysplasia type II, and describe the radiological, electrophysiological, and histopathological findings of our case.
ACTA MEDICA OKAYAMA
(2022)
Review
Clinical Neurology
Horst Urbach, Elias Kellner, Nico Kremers, Ingmar Bluemcke, Theo Demerath
Summary: FCD is classified into different types, with only FCD II showing distinctive MRI and molecular genetic alterations. Subtle FCD located in the depth of sulci are often overlooked and require the use of specialized sequences and postprocessing methods for diagnosis. The added value of 7 Tesla MRI has yet to be proven.
Article
Clinical Neurology
Yao-Feng Li, Fatma Scerif, Simon R. Picker, Thomas J. Stone, Jessica C. Pickles, Dale A. Moulding, Aimee Avery, Alex Virasami, Amy R. Fairchild, Martin Tisdall, William Harkness, J. Helen Cross, Darren Hargrave, Francois Guillemot, Simon M. Paine, Shireena A. Yasin, Thomas S. Jacques
Summary: This study identified previously uncharacterised small cell populations in FCD and TS, highlighting a new level of diversity and cellular interactions in cortical malformations. The findings provide a generalisable approach to understanding cell-cell interactions and cellular heterogeneity in developmental neuropathology.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2021)
Article
Clinical Neurology
Hyo M. Lee, Seok-Jun Hong, Ravnoor Gill, Benoit Caldairou, Irene Wang, Jian-guo Zhang, Francesco Deleo, Dewi Schrader, Fabrice Bartolomei, Maxime Guye, Kyoo Ho Cho, Carmen Barba, Sanjay Sisodiya, Graeme Jackson, R. Edward Hogan, Lily Wong-Kisiel, Gregory D. Cascino, Andreas Schulze-Bonhage, Iscia Lopes-Cendes, Fernando Cendes, Renzo Guerrini, Boris Bernhardt, Neda Bernasconi, Andrea Bernasconi
Summary: This study explores the associations between Focal cortical dysplasia (FCD) and cytoarchitecture, gene expression, and axes of cortical organization. The findings suggest that the vulnerability of the frontal lobe to FCD may be due to early termination of prenatal neurogenesis and aberrant postnatal synaptogenesis.
Article
Radiology, Nuclear Medicine & Medical Imaging
Antonio Giulio Gennari, Dorottya Cserpan, Ilona Stefanos-Yakoub, Raimund Kottke, Ruth O'Gorman Tuura, Georgia Ramantani
Summary: This study investigated the potential of diffusion tensor imaging (DTI) in paediatric structural epilepsy associated with focal cortical dysplasia (FCD). The results showed that DTI indices can differentiate between FCD and contralateral brain parenchyma (CBP), and that clinical features have an impact on these indices.
INSIGHTS INTO IMAGING
(2023)
Article
Clinical Neurology
Horst Urbach, Marcel Heers, Dirk-Matthias Altenmueller, Andreas Schulze-Bonhage, Anke Maren Staack, Thomas Bast, Marco Reisert, Ralf Schwarzwald, Christoph P. Kaller, Hans-Juergen Huppertz, Theo Demerath
Summary: Automated MRI postprocessing tool was evaluated for enhanced and rapid detection of focal cortical dysplasia (FCD). The results showed effective identification of FCD within a minute, with a need for careful comparison with conventional MRI images to reduce false positives.
Article
Neurosciences
Mengyi Guo, Jing Zhang, Jing Wang, Xiongfei Wang, Qing Gao, Chongyang Tang, Jiahui Deng, Zhonghua Xiong, Xiangru Kong, Yuguang Guan, Jian Zhou, Detlev Boison, Guoming Luan, Tianfu Li
Summary: In this study, the adenosine signaling in FCD type I and type II patients was analyzed, revealing upregulation of adenosine-metabolizing enzymes ADK and ADA, as well as adenosine-producing enzyme CD73 in BCs. Moreover, an increase in A(2A)R density, a decrease in GLT-1 levels, and an increase in mTOR levels were observed in FCD specimens. These findings suggest that dysregulation of the adenosine system is a common pathological feature of both FCD type I and type II, and may serve as a therapeutic target for epilepsy associated with FCD.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Clinical Neurology
Hannah Spitzer, Mathilde Ripart, Kirstie Whitaker, Felice D'Arco, Kshitij Mankad, Andrew A. Chen, Antonio Napolitano, Luca De Palma, Alessandro De Benedictis, Stephen Foldes, Zachary Humphreys, Kai Zhang, Wenhan Hu, Jiajie Mo, Marcus Likeman, Shirin Davies, Christopher Guttler, Matteo Lenge, Nathan T. Cohen, Yingying Tang, Shan Wang, Aswin Chari, Martin Tisdall, Nuria Bargallo, Estefania Conde-Blanco, Jose Carlos Pariente, Saul Pascual-Diaz, Ignacio Delgado-Martinez, Carmen Perez-Enriquez, Ilaria Lagorio, Eugenio Abela, Nandini Mullatti, Jonathan O'Muircheartaigh, Katy Vecchiato, Yawu Liu, Maria Eugenia Caligiuri, Ben Sinclair, Lucy Vivash, Anna Willard, Jothy Kandasamy, Ailsa McLellan, Drahoslav Sokol, Mira Semmelroch, Ane G. Kloster, Giske Opheim, Leticia Ribeiro, Clarissa Yasuda, Camilla Rossi-Espagnet, Khalid Hamandi, Anna Tietze, Carmen Barba, Renzo Guerrini, William Davis Gaillard, Xiaozhen You, Irene Wang, Sofia Gonzalez-Ortiz, Mariasavina Severino, Pasquale Striano, Domenico Tortora, Reetta Kalviainen, Antonio Gambardella, Angelo Labate, Patricia Desmond, Elaine Lui, Terence O'Brien, Jay Shetty, Graeme Jackson, John S. Duncan, Gavin P. Winston, Lars H. Pinborg, Fernando Cendes, Fabian J. Theis, Russell T. Shinohara, J. Helen Cross, Torsten Baldeweg, Sophie Adler, Konrad Wagstyl
Summary: One of the challenges in applying machine learning to diagnostic biomedical imaging is the interpretability of algorithms. This study developed an open-source and interpretable machine-learning algorithm to automatically identify FCDs from structural MRI data, improving the confidence of physicians in identifying subtle MRI lesions in individuals with epilepsy.
Article
Clinical Neurology
Julius Dengler, Daniel Ruefenacht, Bernhard Meyer, Veit Rohde, Matthias Endres, Pavlina Lenga, Konstantin Uttinger, Viktoria Ruecker, Maria Wostrack, Adisa Kursumovic, Bujung Hong, Dorothee Mielke, Nils Ole Schmidt, Jan-Karl Burkhardt, Philippe Bijlenga, Edoardo Boccardi, Christophe Cognard, Peter U. Heuschmann, Peter Vajkoczy
Summary: Limited clinical evidence exists on giant intracranial aneurysms (GIAs), with a focus on their natural history, case fatality, and treatment outcomes for both ruptured and unruptured cases. Both ruptured and unruptured GIAs displayed poor prognosis, with high rupture rates in the unruptured cases. Patients undergoing surgical or endovascular treatment had lower case fatality and rupture rates compared to those receiving conservative management, likely due to differences in patient selection criteria.
JOURNAL OF NEUROSURGERY
(2021)
Article
Clinical Neurology
Julika Pitsch, Karen M. J. van Loo, Marco Gallus, Andre Dik, Delara Kamalizade, Ann-Kathrin Baumgart, Vadym Gnatkovsky, Johannes Alexander Mueller, Thoralf Opitz, Gordon Hicking, Venu Narayanan Naik, Lydia Wachsmuth, Cornelius Faber, Rainer Surges, Christian Kurts, Susanne Schoch, Nico Melzer, Albert J. Becker
Summary: The study demonstrates that the attack of specific hippocampal neurons by CD8(+) T cells is sufficient to induce limbic encephalitis (LE) converting into temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS), highlighting the major pathogenic role of CD8(+) T cells beyond neurotoxic effects.
ANNALS OF NEUROLOGY
(2021)
Article
Multidisciplinary Sciences
Miguel Rodriguez de Los Santos, Marion Rivalan, Friederike S. David, Alexander Stumpf, Julika Pitsch, Despina Tsortouktzidis, Laura Moreno Velasquez, Anne Voigt, Karl Schilling, Daniele Mattei, Melissa Long, Guido Vogt, Alexej Knaus, Bjorn Fischer-Zirnsak, Lars Wittler, Bernd Timmermann, Peter N. Robinson, Denise Horn, Stefan Mundlos, Uwe Kornak, Albert J. Becker, Dietmar Schmitz, York Winter, Peter M. Krawitz
Summary: Pathogenic germline mutations in PIGV lead to glycosylphosphatidylinositol biosynthesis deficiency (GPIBD). By introducing the prevalent hypomorphic missense mutation found in European patients into mice, researchers successfully created a mouse model that mirrors the cognitive impairments, motor deficits, and other symptoms observed in human patients. The study provides insights into the pathophysiology of GPIBD and the role of GPI-anchor-related pathways in brain development.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Sami Ridwan, Alexander Grote, Matthias Simon
Summary: The study observed that peak levels of IL-6 in the cerebrospinal fluid (CSF) of patients with severe aneurysmal subarachnoid hemorrhage (SAH) occurred between days 4 and 14 after SAH, with significant correlations to delayed cerebral ischemia (DCI) and infarctions. Elevated CSF IL-6 levels may serve as a potential biomarker for DCI with infarction, but individual variations limit its diagnostic utility in SAH patients.
SCIENTIFIC REPORTS
(2021)
Review
Biochemistry & Molecular Biology
Matthias Simon, Alexander Grote
Summary: IL-6 is a proinflammatory cytokine that may serve as a potential biomarker in SAH patients, although discrepancies in research findings and lack of defined clinical endpoints hinder its routine clinical use. Further research is needed to better understand the role of IL-6 and neuroinflammation in the pathophysiology of SAH.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Susanne Schoch, Anne Quatraccioni, Barbara K. Robens, Robert Maresch, Karen M. J. van Loo, Silvia Cases-Cunillera, Tony Kelly, Thoralf Opitz, Valeri Borger, Dirk Dietrich, Julika Pitsch, Heinz Beck, Albert J. Becker
Summary: SLK plays a critical role in the development of cortical neurons in mice, specifically in the elaboration of higher dendrites and maintaining the balance between excitation and inhibition. Knockdown of SLK leads to loss of inhibitory synapses and functional inhibition in mouse neurons, with potential relevance to human cortical malformations.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Clinical Neurology
Annika Reimers, Chiara A. Hummel, Anna Maria Eis-Huebinger, Rainer Surges, Pitt Niehusmann, Susanne Schoch, Albert J. Becker, Julika Pitsch
Summary: The study found a higher incidence of specific autoantibodies in adults with early diagnosis of possible limbic encephalitis (LE). Anti-LGI1 antibodies were significantly more frequent in the early diagnosis group compared to the late diagnosis group. Viral HHV-6 DNA was only detected in one serum sample of the early diagnosis group, with no evidence in the late diagnosis group.
Article
Oncology
Tunc Faik Ersoy, Neda Mokhtari, Daniel Brainman, Bjoern Berger, Attila Salay, Philipp Schuett, Florian Weissinger, Alexander Grote, Matthias Simon
Summary: Cerebellar metastases patients have varying prognoses and individualized decision-making is crucial. Chemotherapy has a positive impact on survival, while extracerebral metastases do not significantly influence overall survival.
Article
Surgery
Sami Ridwan, Mario Ganau, Cesare Zoia, Marike Broekman, Alexander Grote, Hans Clusmann
Summary: This study investigated the impact of COVID-19 on international neurosurgeons, revealing a significant decrease in surgical activity due to the pandemic. While most neurosurgeons expressed concerns about personal and family health, private practitioners faced uncertain financial outlooks during the ongoing crisis.
FRONTIERS IN SURGERY
(2021)
Article
Oncology
Nancy Ann Oberheim-Bush, Wenyin Shi, Michael W. McDermott, Alexander Grote, Julia Stindl, Leonardo Lustgarten
Summary: This study evaluated the safety of TTFields therapy in patients with GBM and a VP shunt. Results showed that TTFields therapy was well tolerated and had a favorable safety profile in this population. There was no evidence of disruption to VP shunt effectiveness with TTFields therapy.
JOURNAL OF NEURO-ONCOLOGY
(2022)
Article
Clinical Neurology
Eric Goulin Lippi Fernandes, Sami Ridwan, Isabell Greeve, Wolf-Ruediger Schaebitz, Alexander Grote, Matthias Simon
Summary: This study analyzed the clinical and imaging data of 49 patients who underwent posterior fossa decompression surgery for cerebellar infarction. The results showed that rapid recovery of consciousness after surgery does not necessarily lead to good functional outcomes. While many patients died during follow-up, long-term functional impairment was rare. Surgical intervention should focus primarily on pressure relief, and the removal of infarcted tissue may have limited impact on outcomes. Patients with a Glasgow Coma Scale (GCS) of 14-15 may be able to postpone surgery.
FRONTIERS IN NEUROLOGY
(2022)
Article
Clinical Neurology
Alexander Grote, Dieter-Henrik Heiland, Julia Taube, Christoph Helmstaedter, Vidhya M. Ravi, Paulina Will, Elke Hattingen, Jan-Ruediger Schuere, Juri-Alexander Witt, Annika Reimers, Christian Elger, Johannes Schramm, Albert J. Becker, Daniel Delev
Summary: This study identifies a distinct mesial-temporal lobe epilepsy syndrome called "innate inflammatory gliosis only" characterized by chronic inflammation associated with astrocytes. Patients with this syndrome have poor seizure and neuropsychological outcomes after surgery compared to patients with hippocampus sclerosis. The findings suggest that this syndrome requires innovative pharmacotreatment strategies.
Article
Biochemistry & Molecular Biology
Juergen Serth, Inga Peters, Olga Katzendorn, Tu N. Dang, Joana Moog, Zarife Balli, Christel Reese, Joerg Hennenlotter, Alexander Grote, Marcel Lafos, Hossein Tezval, Markus A. Kuczyk
Summary: Recent studies have shown that DNA methylation of the NKX6-2 gene can be used to predict the risk of metastatic disease in RCC patients, with NKX6-2 found to be hypermethylated in primary metastatic RCC. Analysis of methylation data from different tissue samples reveals similarities between metastatic tissues and primary metastatic RCC tissues.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Julia Taube, Juri-Alexander Witt, Alexander Grote, Daniel Delev, Jonas Enkirch, Elke Hattingen, Albert J. Becker, Christian Erich Elger, Christoph Helmstaedter
Summary: This study compared the pre- and postoperative memory performance of patients with gliosis only (GO) and hippocampal sclerosis (HS). The results showed that GO patients had a later onset of epilepsy, less severe and non-specific memory impairments before surgery, less successful surgical outcome, and a more significant memory decline after surgery compared to HS patients. These findings provide further evidence that GO and HS are distinct clinical entities.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Meeting Abstract
Oncology
Nancy Ann Oberheim-Bush, Wenyin Shi, Michael McDermott, Alexander Grote, Julia Stindl, Leonardo Lustgarten
Article
Neurosciences
Nihal A. Salem, Lawrence Manzano, Michael W. Keist, Olga Ponomareva, Amanda J. Roberts, Marisa Roberto, R. Dayne Mayfield
Summary: This study identified cell-type specific gene expression changes associated with alcohol dependence in the medial prefrontal cortex of mice. The results revealed dysregulated gene co-expression networks and differentially expressed genes in multiple cell types, highlighting the involvement of inhibitory neurons and astrocytes in alcohol dependence. Novel targets for studying molecular mechanisms contributing to alcohol dependence were also identified.
NEUROBIOLOGY OF DISEASE
(2024)
Article
Neurosciences
Laura E. Hawley, Megan Stringer, Abigail J. Deal, Andrew Folz, Charles R. Goodlett, Randall J. Roper
Summary: This study found that the overexpression of DYRK1A protein in Down syndrome mice varies with age, sex, and brain region, and reducing the copy number of Dyrk1a can decrease the expression of DYRK1A. These sex-specific patterns of DYRK1A overexpression may provide mechanistic targets for therapeutic intervention in Down syndrome.
NEUROBIOLOGY OF DISEASE
(2024)