Article
Neurosciences
Delphine Hardy, Emmanuelle Buhler, Dmitrii Suchkov, Antonin Vinck, Aurelien Fortoul, Francoise Watrin, Alfonso Represa, Marat Minlebaev, Jean-Bernard Manent
Summary: Malformations of cortical development are a major cause of childhood epilepsy, but their patho-logical substrate and dynamic changes leading to epilepsy are not well understood. In this study, a rat model of subcortical band heterotopia (SBH), a type of cortical malformation associated with drug-resistant seizures in humans, was characterized. Longitudinal electrographic recordings were used to monitor the age-dependent evolution of epileptiform discharges in this model. The study found age-related changes in seizure properties and patterns, indicating a gradual progression towards adult seizure patterns. The study also identified the contributions of SBH and the overlying cortex to the development and age-dependent progression of epilepsy. It was found that early suppression of neuronal excitability in SBH can slow down epileptogenesis, while suppression of excitability in the overlying cortex paradoxically exacerbates epileptogenesis. However, such manipulations have no effect on chronic spontaneous seizures. These findings provide insights into the complex developmental alterations in SBH and the overlying cortex that contribute to the generation of pathogenic circuits prone to seizures and suggest that early and targeted interventions could modify the course of epilepsy in cortical malformations.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Clinical Neurology
R. A. Hickman, P. L. Faust, M. K. Rosenblum, K. Marder, M. F. Mehler, J. P. Vonsattel
Summary: This study found a higher occurrence of developmental malformations in the brains of Huntington Disease (HD) patients, possibly due to the impact of HTT gene expansion on neuronal precursors susceptibility to somatic mutations.
ACTA NEUROPATHOLOGICA
(2021)
Review
Clinical Neurology
Ayush Khandelwal, Ankita Aggarwal, Anuradha Sharma, Amita Malik, Anindita Bose, Ankita Aggarwal
Summary: This article provides an overview of the structural anomalies and clinical manifestations of malformations of cortical development (MCDs), highlights the importance of neuroimaging in the diagnostic process, and includes a table summarizing the embryologic, clinical, and genetic findings associated with various MCDs.
WORLD NEUROSURGERY
(2022)
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
Neurosciences
Dan-Dan Wang, Mitali Katoch, Samir Jabari, Ingmar Blumcke, David B. B. Blumenthal, De-Hong Lu, Roland Coras, Yu-Jiao Wang, Jie Shi, Wen-Jing Zhou, Katja Kobow, Yue-Shan Piao
Summary: Focal Cortical Dysplasia (FCD) is a common cause of drug-resistant focal epilepsy in children and young adults. This study investigated the DNA methylation signature of a new subtype of FCD 3D and found distinct differences in DNA methylation patterns compared to other FCD subtypes or controls. The DNA methylation signature in FCD 3D was associated with specific histopathology subtypes and biological pathways related to neurodegeneration and cytoskeleton regulation. These findings suggest the importance of DNA methylation in cortical malformations and its relevance to epilepsy.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Clinical Neurology
Hajime Miyata, Haruka Kuwashige, Tomokatsu Hori, Yuichi Kubota, Tom Pieper, Roland Coras, Ingmar Blumcke, Yasuji Yoshida
Summary: Research has found that FCD-IIIc has specific histopathological characteristics in epilepsy-associated vascular malformations, which may depend on the type and developmental timing of the vascular malformation.
Article
Clinical Neurology
Ariadne Zampeli, Boel Hansson, Karin Markenroth Bloch, Elisabet Englund, Kristina Kallen, Maria Compagno Strandberg, Isabella M. Bjorkman-Burtscher
Summary: This study analyzed the structural characteristics of malformations of cortical development (MCD) using 7T and 3T MRI and found that 7T MRI can reveal subtle connections between heterotopia and previously unidentified pathology in overlaying cortex.
SEIZURE-EUROPEAN JOURNAL OF EPILEPSY
(2022)
Article
Biochemistry & Molecular Biology
Yan-Ting Lu, Chung-Yao Hsu, Yo-Tsen Liu, Chung -Kin Chan, Yao-Chung Chuang, Chih-Hsiang Lin, Kai-Ping Chang, Chen-Jui Ho, Ching -Ching Ng, Kheng-Seang Lim, Meng -Han Tsai
Summary: This study aims to delineate the clinical and imaging spectrum that differentiates FLNA-positive and FLNA-negative PVNH patients. The results showed that FLNA mutations accounted for less than half of the PVNH patients, and FLNA-positive patients were more likely to have extra-cerebral features compared with FLNA-negative patients.
BIOMEDICAL JOURNAL
(2022)
Article
Neurosciences
Adi Miriam Goldenberg, Sarah Schmidt, Rea Mitelman, Dana Rubi Levy, Matthias Prigge, Yonatan Katz, Ofer Yizhar, Heinz Beck, Ilan Lampl
Summary: Focal cortical epilepsies are difficult to treat due to the lack of reliable animal models. In this study, the researchers successfully induced epileptiform events by selectively expressing the inhibitory receptor hM4D in GABAergic neurons in focal cortical areas. The model showed reliable induction of high-frequency oscillations and propagation of epileptiform events.
Article
Neurosciences
Marco de Curtis, Laura Librizzi, Laura Uva
Summary: Seizures affecting the limbic regions, such as the hippocampus, are common and often resistant to medication. This study examines the network mechanisms involved in the generation of olfactory-limbic epileptiform patterns and discusses the potential relevance of these findings for human focal epilepsy. The interactions within olfactory-limbic circuits, including region-specific seizure-like events and cortical control, are investigated using in vitro preparations and pro-convulsive drugs.
NEUROBIOLOGY OF DISEASE
(2023)
Review
Medicine, General & Internal
Dimitar Metodiev, Krassimir Minkin, Margarita Ruseva, Rumiana Ganeva, Dimitar Parvanov, Sevdalin Nachev
Summary: This article reviews the literature on the morphological changes associated with pharmacoresistant epilepsy, emphasizing the morphological basis in brain tissue. The International League Against Epilepsy (ILAE) has revised the classification of FCD and introduced new histologically defined pathological entities. Although the pathomorphological characteristics of various forms of focal cortical dysplasias are well known, their etiology and pathogenesis remain unclear. The identification of genetic variants in FCD opens up new treatment strategies.
Article
Multidisciplinary Sciences
Alan J. Emanuel, Brendan P. Lehnert, Stefano Panzeri, Christopher D. Harvey, David D. Ginty
Summary: Research shows that signals from physiologically distinct mechanoreceptor subtypes are extensively integrated and transformed within the subcortical somatosensory system to generate cortical representations of touch.
Article
Computer Science, Artificial Intelligence
Jorg Vorndran, Christoph Neuner, Roland Coras, Lucas Hoffmann, Simon Geffers, Jonas Honke, Jochen Herms, Sigrun Roeber, Hajo Hamer, Sebastian Brandner, Till Hartlieb, Tom Pieper, Manfred Kudernatsch, Christian G. Bien, Thilo Kalbhenn, Matthias Simon, Homa Adle-Biassette, Jesus Cienfuegos, Roberta Di Giacomo, Rita Garbelli, Hajime Miyata, Angelika Muhlebner, Savo Raicevic, Tuomas Rauramaa, Fabio Rogerio, Ingmar Bluemcke, Samir Jabari
Summary: A deep learning-based classifier has been developed to histopathologically diagnose human brain specimens obtained from epilepsy surgery, which helps confirm the underlying cause of focal epilepsy and guide postsurgical patient management. The classifier can automatically recognize different subtypes of Focal Cortical Dysplasia (FCD) with high accuracy. This will aid in the differential histopathology diagnosis of neocortical specimens in epilepsy surgery.
NEURAL COMPUTING & APPLICATIONS
(2023)
Article
Neurosciences
Heiko J. Luhmann
Summary: This review article provides an overview of the molecular, cellular, and network mechanisms underlying focal seizures in neocortical networks with developmental malformations. Neocortical malformations are a large variety of structural abnormalities associated with epilepsy and other neurological and psychiatric disorders. Animal models and state-of-the-art techniques have contributed to our understanding of neocortical hyperexcitability in developmental disorders. Additionally, molecular biological and electro-physiological techniques have provided insights into the subcellular, cellular, and network mechanisms of focal seizures.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Clinical Neurology
Jose A. Graterol Perez, Stephanie Guder, Chi-Un Choe, Christian Gerloff, Robert Schulz
Summary: This study found that stroke patients exhibited significantly reduced cortical thickness not only in the ipsilesional primary motor cortex but also in numerous secondary motor and non-motor brain regions. However, there was no significant relationship between the extent of cortical thickness reduction and stroke-related excitability changes of the motor network or clinical scores.
FRONTIERS IN NEUROLOGY
(2022)
Article
Clinical Neurology
Jolina Lombardi, Benjamin Mayer, Elisa Semler, Sarah Anderl-Straub, Ingo Uttner, Jan Kassubek, Janine Diehl-Schmid, Adrian Danek, Johannes Levin, Klaus Fassbender, Klaus Fliessbach, Anja Schneider, Hans-Juergen Huppertz, Holger Jahn, Alexander Volk, Johannes Kornhuber, Bernhard Landwehrmeyer, Martin Lauer, Johannes Prudlo, Jens Wiltfang, Matthias L. Schroeter, Albert Ludolph, Markus Otto
Summary: PPA is a left-dominant disease with significant atrophy at baseline, primarily affecting gray matter and progressing in a variant-specific manner. The highest atrophy at baseline was found in the left frontal lobe for nfvPPA, left temporal lobe for svPPA, and (medial) temporal regions for lvPPA, with different patterns of progression within 1-year follow-up.
ALZHEIMERS & DEMENTIA
(2021)
Review
Clinical Neurology
Christina Wittke, Sonja Petkovic, Valerija Dobricic, Susen Schaake, Gesine Respondek, Anne Weissbach, Harutyun Madoev, Joanne Trinh, Eva-Juliane Vollstedt, Neele Kuhnke, Katja Lohmann, Marija Dulovic Mahlow, Connie Marras, Inke R. Koenig, Maria Stamelou, Vincenzo Bonifati, Christina M. Lill, Meike Kasten, Hans-Jurgen Huppertz, Guenter Hoeglinger, Christine Klein
Summary: This systematic review focuses on monogenic atypical parkinsonism with mutations in specific genes. An automated classification procedure was used to distinguish the different forms of monogenic atypical parkinsonism with high accuracy. Patients with monogenic atypical parkinsonism showed earlier onset and less favorable levodopa response compared to those with monogenic typical presentations.
MOVEMENT DISORDERS
(2021)
Article
Neurosciences
Hans-Peter Mueller, Anna Behler, G. Bernhard Landwehrmeyer, Hans-Juergen Huppertz, Jan Kassubek
Summary: This theoretical study explores the impact of time-intervals in longitudinal imaging studies with one baseline and two follow-up visits on the results. Suggestions for analyzing longitudinal trends are provided based on simulations and analysis of atlas-based volumetry data of Huntington's disease patients.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Clinical Neurology
Theo Demerath, Christoph P. Kaller, Marcel Heers, Anke Staack, Ralf Schwarzwald, Tobias Kober, Marco Reisert, Andreas Schulze-Bonhage, Hans-Juergen Huppertz, Horst Urbach
Summary: The study showed that utilizing MP2RAGE sequences for FCD detection had higher sensitivity compared to using MPRAGE sequences. Additionally, incorporating cluster volume information helped differentiate between true and false positive results in MP2RAGE imaging.
Article
Clinical Neurology
Angela Rosenbohm, Kelly Del Tredici, Heiko Braak, Hans-Juergen Huppertz, Albert C. Ludolph, Hans-Peter Mueller, Jan Kassubek
Summary: The study utilized DTI data to investigate specific white matter alterations in flail arm syndrome patients, showing similarities in white matter integrity with 'classical' ALS patients. The results support the hypothesis that flail arm syndrome is a phenotypical variant of ALS.
JOURNAL OF NEUROLOGY
(2022)
Review
Clinical Neurology
Anne Weissbach, Martje G. Pauly, Rebecca Herzog, Lisa Hahn, Sara Halmans, Feline Hamami, Christina Bolte, Sarah Camargos, Beomseok Jeon, Manju A. Kurian, Thomas Opladen, Norbert Brueggemann, Hans-Juergen Huppertz, Inke R. Koenig, Christine Klein, Katja Lohmann
Summary: By analyzing a large number of DRD patients and asymptomatic GCH1 mutation carriers, specific phenotypic and biochemical characteristics were identified, which can aid in the rapid diagnosis and initiation of treatment.
MOVEMENT DISORDERS
(2022)
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
Clinical Neurology
Leonie Lampe, Sebastian Niehaus, Hans-Juergen Huppertz, Alberto Merola, Janis Reinelt, Karsten Mueller, Sarah Anderl-Straub, Klaus Fassbender, Klaus Fliessbach, Holger Jahn, Johannes Kornhuber, Martin Lauer, Johannes Prudlo, Anja Schneider, Matthis Synofzik, Adrian Danek, Janine Diehl-Schmid, Markus Otto, Arno Villringer, Karl Egger, Elke Hattingen, Rudiger Hilker-Roggendorf, Alfons Schnitzler, Martin Sudmeyer, Wolfgang Oertel, Jan Kassubek, Gunter Hoeglinger, Matthias L. Schroeter
Summary: This study compared several machine learning methods for the classification of neurodegenerative diseases based on structural magnetic resonance imaging. The results showed that the neural network performed the best and most consistently, while the ensemble learning methods or support vector machine had better performance for smaller classes.
ALZHEIMERS RESEARCH & THERAPY
(2022)
Article
Genetics & Heredity
Randi von Wrede, Martin Schidlowski, Hans-Juergen Huppertz, Theodor Rueber, Anja Ivo, Tobias Baumgartner, Kerstin Hallmann, Gabor Zsurka, Christoph Helmstaedter, Rainer Surges, Wolfram S. Kunz
Summary: In this study, we identified a novel homozygous frame-shift mutation in ASPM gene in a consanguineous family, leading to microcephaly, epilepsy, and cognitive deficits. Our findings suggest that the severity of neurological symptoms in patients with ASPM mutations may be influenced by factors other than ASPM expression levels.
Article
Clinical Neurology
Patrick Oeckl, Sarah Anderl-Straub, Adrian Danek, Janine Diehl-Schmid, Klaus Fassbender, Klaus Fliessbach, Steffen Halbgebauer, Hans-Juergen Huppertz, Holger Jahn, Jan Kassubek, Johannes Kornhuber, Bernhard Landwehrmeyer, Martin Lauer, Johannes Prudlo, Anja Schneider, Matthias L. Schroeter, Petra Steinacker, Alexander E. Volk, Matias Wagner, Juliane Winkelmann, Jens Wiltfang, Albert C. Ludolph, Markus Otto
Summary: Recent data support beta-synuclein as a blood biomarker for studying synaptic degeneration in Alzheimer's disease. This study compared serum beta-synuclein with established blood markers (p-tau181 and NfL) and found that beta-synuclein is increased in AD and correlated with temporal brain atrophy and cognitive impairment. The pattern of beta-synuclein changes differs from p-tau181 and NfL.
ALZHEIMERS & DEMENTIA
(2023)
Review
Clinical Neurology
Lennart Walger, Sophie Adler, Konrad Wagstyl, Leonie Henschel, Bastian David, Valeri Borger, Elke Hattingen, Hartmut Vatter, Christian E. Elger, Torsten Baldeweg, Felix Rosenow, Horst Urbach, Albert Becker, Alexander Radbruch, Rainer Surges, Martin Reuter, Fernando Cendes, Zhong Irene Wang, Hans-Juergen Huppertz, Theodor Rueber
Summary: Focal cortical dysplasias (FCDs) are common pathologies causing treatment-resistant focal epilepsy. Resective neurosurgery can be successful, but the visual assessment of magnetic resonance imaging is not always accurate in locating FCDs. Computational approaches using artificial intelligence show promise in automatic FCD detection. However, challenges remain in organizing imaging data, evaluating algorithmic output, and making research accessible and reproducible.
Article
Neuroimaging
Leonie Lampe, Hans-Jurgen Huppertz, Sarah Anderl-Straub, Franziska Albrecht, Tommaso Ballarini, Sandrine Bisenius, Karsten Mueller, Sebastian Niehaus, Klaus Fassbender, Klaus Fliessbach, Holger Jahn, Johannes Kornhuber, Martin Lauer, Johannes Prudlo, Anja Schneider, Matthis Synofzik, Jan Kassubek, Adrian Danek, Arno Villringer, Janine Diehl-Schmid, Markus Otto, Matthias L. Schroeter
Summary: The study aimed to build a classifier for multiple dementia syndromes using MRI, and the results showed that the binary classification models achieved high prediction accuracies between 71% and 95%, with disease-specific atrophy patterns reflected in feature importance. The multi-syndrome model reached accuracies more than three times higher than chance level but was still far from 100%, and the performance varied across different dementia syndromes.
NEUROIMAGE-CLINICAL
(2023)
Article
Clinical Neurology
Horst Urbach, Christian Scheiwe, Muskesh J. J. Shah, Julia M. M. Nakagawa, Marcel Heers, Maria Victoria San Antonio-Arce, Dirk-Matthias Altenmueller, Andreas Schulze-Bonhage, Hans-Juergen Huppertz, Theo Demerath, Soroush Doostkam
Summary: The purpose of this study was to evaluate the diagnostic accuracy of epilepsy-dedicated 3 Tesla MRI by correlating MRI, histopathology, and postsurgical seizure outcomes. The results showed that MRI and histopathology were concordant in most cases, but there were some cases where MRI missed certain lesions or showed false positives. The proposed MRI protocol was found to be highly accurate overall.
CLINICAL NEURORADIOLOGY
(2023)
Article
Clinical Neurology
Mike Wattjes, Hans-Juergen Huppertz, Nima Mahmoudi, Sophia Stoecklein, Sophia Rogozinski, Florian Wegner, Martin Klietz, Ivayla Apostolova, Johannes Levin, Sabrina Katzdobler, Carsten Buhmann, Andrea Quattrone, Georg Berding, Matthias Brendel, Henryk Barthel, Osama Sabri, Guenter Hoeglinger, Ralph Buchert, Alzheimers Dis Neuroimaging Initiat
Summary: This study compared the value of different MRI reading strategies and automatic classification methods in the diagnosis of PSP. The results showed that the fully automatic classification method using support vector machine performed the best, especially in the diagnosis of vPSP. Therefore, it is recommended to use machine learning methods for fully automatic classification in settings with a broad phenotypic PSP spectrum.
MOVEMENT DISORDERS
(2023)
Article
Clinical Neurology
Ralph Buchert, Florian Wegner, Hans-Juergen Huppertz, Georg Berding, Matthias Brendel, Ivayla Apostolova, Carsten Buhmann, Alexander Dierks, Sabrina Katzdobler, Martin Klietz, Johannes Levin, Nima Mahmoudi, Andreas Rinscheid, Sophia Rogozinski, Jost-Julian Rumpf, Christine Schneider, Sophia Stoecklein, Phoebe G. Spetsieris, David Eidelberg, Mike P. Wattjes, Osama Sabri, Henryk Barthel, Guenter Hoeglinger
Summary: This study evaluated FDG-PET in a sample of 41 PSP patients and found that automatic covariance pattern analysis outperformed visual interpretation in detecting PSP-RS and provided useful sensitivity for vPSP. Pattern expression analysis is clinically useful in suspected PSP to complement visual reading and voxel-based testing.
MOVEMENT DISORDERS
(2023)