Article
Biochemistry & Molecular Biology
Rie Komori, Taira Matsuo, Aya Yokota-Nakatsuma, Ritsuka Hashimoto, Shizuka Kubo, Chihiro Kozawa, Tomomi Kono, Yasuhiro Ishihara, Kouichi Itoh
Summary: Levetiracetam suppresses neuroinflammation and prevents epilepsy onset by inhibiting the expression of Fosl1, which regulates astrocyte reactivity during epileptogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Amanda Larissa Dias Pacheco, Igor Santana de Melo, Maisa de Araujo Costa, Mariah Morais Celestino Amaral, Nivea Karla de Gusmao Taveiros Silva, Yngrid Mickaelli Oliveira Santos, Daniel Leite Goes Gitai, Marcelo Duzzioni, Alexandre Urban Borbely, Robinson Sabino Silva, Ana Luiza Ferreira Donatti, Luisa Mestriner, Carlos Alessandro Fuzo, Richard D. Cummings, Norberto Garcia-Cairasco, Marcelo Dias-Baruffi, Olagide Wagner de Castro
Summary: Administration of GAL-1 reduces the severity of seizures, inflammation, and neurodegeneration, suggesting a neuroprotective effect in the early stage of epileptogenesis.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Neurosciences
Sayed Mostafa Modarres Mousavi, Fatemeh Alipour, Farshid Noorbakhsh, Maryam Jafarian, Masoud Ghadipasha, Jaber Gharehdaghi, Christoph Kellinghaus, Erwin-Josef Speckmann, Walter Stummer, Maryam Khaleghi Ghadiri, Ali Gorji
Summary: Widespread alterations in gene expression may contribute to epilepsy pathogenesis. We evaluated the expression levels of various genes in the epileptic hippocampus and amygdala, compared to autopsy controls, and assessed the correlation between molecular alterations and clinical characteristics in patients undergoing epilepsy surgery. Significant and complex changes in key regulatory genes were found in both the hippocampus and amygdala of patients with intractable epilepsy. The expression changes varied between the two regions and different correlation patterns were observed depending on patient grouping.
MOLECULAR NEUROBIOLOGY
(2023)
Review
Pharmacology & Pharmacy
Christian Holscher
Summary: Type 2 diabetes and insulin desensitization have been linked to neurodegenerative disorders like Alzheimer's and Parkinson's diseases. GLP-1 and GIP hormones have shown neuroprotective effects in trials, suggesting potential disease-modifying care for patients.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Danylo Batulin, Fereshteh Lagzi, Annamaria Vezzani, Peter Jedlicka, Jochen Triesch
Summary: The study presents a mathematical model to understand the complex processes involved in the development of epilepsy. The model successfully describes the characteristics of epileptogenesis and can be used to predict therapeutic strategies.
Editorial Material
Immunology
Cecilia Garlanda, Domenico Supino
Summary: The researchers in this study designed a new drug to selectively inhibit IL-1 by analyzing an IL-1 receptor missense mutation associated with un-leashed IL-1-mediated inflammation.
Review
Clinical Neurology
Lei Sun, Wei Shan, Huajun Yang, Ru Liu, Jianping Wu, Qun Wang
Summary: Post-traumatic epilepsy is a serious consequence of traumatic brain injury, and inflammation plays a significant role in epileptogenesis. Understanding the contribution of neuroinflammation to the development of PTE is crucial, requiring further research.
FRONTIERS IN NEUROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Maria Jose Aguilar-Castillo, Pablo Cabezudo-Garcia, Nicolas Lundahl Ciano-Petersen, Guillermina Garcia-Martin, Marta Marin-Gracia, Guillermo Estivill-Torrus, Pedro Jesus Serrano-Castro
Summary: Neuroinflammation is a common occurrence in various types of epilepsies and recent research has identified key molecular pathways involved in these processes, pointing towards potential future therapeutic targets for epilepsy. Different drugs currently available or in development have shown the ability to inhibit or modulate molecular pathways related to the immunologic or neuroinflammatory mechanisms in epilepsy, suggesting their potential as anti-seizure medications to be tested in the future.
Review
Neurosciences
Toni Christoph Berger, Erik Tauboll, Kjell Heuser
Summary: The current pharmacological therapy for epilepsy is limited to symptomatic treatment, resulting in a high proportion of patients with uncontrolled seizures. Understanding the pathological mechanisms of epileptogenesis could lead to the development of novel treatment strategies. However, the lack of knowledge about molecular upstream mechanisms and involvement of glial cells hinders drug development.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Kamil Kosmider, Maciej Kamieniak, Stanislaw J. Czuczwar, Barbara Miziak
Summary: Epilepsy is a chronic disease that causes recurrent seizures due to excessive oxidants formed during epileptic seizures. This review examines the relationship between newer antiepileptic drugs and oxidative stress. It suggests that drugs enhancing GABA-ergic transmission or other antiepileptics can reduce neuronal oxidation markers, but high doses of GABA-enhancing drugs may increase oxidative stress. Additionally, diazepam has a neuroprotective effect in a U-shaped dose-dependent manner.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Clinical Neurology
Chris G. Dulla, Asla Pitkanen
Summary: Traumatic brain injury (TBI) can lead to post-traumatic epilepsy (PTE) which often resists standard anti-seizure drugs. Novel treatment strategies are needed to prevent PTE after TBI, as there are no successful approaches currently available. TBI presents a unique opportunity for intervention to prevent epileptogenesis, with potential for exciting new advances in the field.
Article
Clinical Neurology
Aurelie Hanin, Jorge Cespedes, Karim Dorgham, Yashwanth Pulluru, Margaret Gopaul, Guy Gorochov, David A. Hafler, Vincent Navarro, Nicolas Gaspard, Lawrence J. Hirsch
Summary: The study aims to investigate inflammation in patients with new-onset refractory status epilepticus (NORSE) by analyzing cytokines/chemokines in cerebrospinal fluid (CSF) and serum. Significant increase of pro-inflammatory cytokines/chemokines was observed in patients with SE compared to those without, and in patients with cNORSE compared to non-cryptogenic RSE. Elevated innate immunity cytokine/chemokine levels were associated with worse short- and long-term outcomes in patients with NORSE.
ANNALS OF NEUROLOGY
(2023)
Article
Pharmacology & Pharmacy
D. Cunha-Reis, A. Caulino-Rocha, P. Correia-de-Sa
Summary: Mesial temporal lobe epilepsy (MTLE) is characterized by seizures originating in the hippocampus or other mesial temporal lobe structures. Potential precipitating events such as trauma, complex febrile seizures, status epilepticus, inflammatory insults, or ischemia have been implicated. New therapeutic strategies aim to prevent epileptogenic processes rather than controlling symptomatic seizures in MTLE.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Allergy
Alexandra Schroeder, Lars P. Lunding, Ulrich M. Zissler, Christina Vock, Sina Webering, Johanna C. Ehlers, Zane Orinska, Adam Chaker, Carsten B. Schmidt-Weber, Niklas J. Lang, Herbert B. Schiller, Marcus A. Mall, Heinz Fehrenbach, Charles A. Dinarello, Michael Wegmann
Summary: The study found that IL-37 downregulates allergic airway inflammation by counterbalancing the disease-amplifying effects of IL-1 beta and IL-33.
Review
Pharmacology & Pharmacy
Xinyi Wang, Zhe Hu, Kai Zhong
Summary: Epilepsy, a common and serious neurological disorder, remains challenging to manage. The role of brain-derived neurotrophic factor (BDNF) in epileptogenesis is still controversial, despite evidence suggesting its importance in the process.
FRONTIERS IN PHARMACOLOGY
(2021)
Editorial Material
Pediatrics
Sampsa Vanhatalo, Nathan J. Stevenson, Ronit M. Pressler, Nicholas S. Abend, Stephane Auvin, Francesco Brigo, M. Roberta Cilio, Cecil D. Hahn, Hans Hartmann, Lena Hellstrom-Westas, Terrie E. Inder, Solomon L. Moshe, Magda L. Nunes, Renee A. Shellhaas, Kollencheri P. Vinayan, Linda S. de Vries, Jo M. Wilmshurst, Elissa Yozawitz, Geraldine B. Boylan
Summary: Brain monitoring plays a crucial role in neonatal neurocritical care, but recent research failed to prove its effectiveness in seizure treatment.
PEDIATRIC RESEARCH
(2023)
Article
Behavioral Sciences
Kim I. Bishop, Peter K. Isquith, Gerard A. Gioia, Kelly G. Knupp, Ingrid E. Scheffer, Rima Nabbout, Nicola Specchio, Joseph Sullivan, Stephane Auvin, J. Helen Cross, Renzo Guerrini, Gail Farfel, Bradley S. Galer, Arnold R. Gammaitoni
Summary: This study aimed to evaluate the association between fenfluramine (FFA) and improvement in everyday executive function (EF) in preschool-aged children with Dravet syndrome (DS). The results showed that the FFA treatment group demonstrated reliable and clinically meaningful improvement in self-control, flexibility, metacognition, and overall executive function. Among the FFA treatment groups, the 0.7 mg/kg/day dosage group showed the most significant improvement.
EPILEPSY & BEHAVIOR
(2023)
Letter
Pediatrics
Manon Casabianca, Julia Roux, Stephane Auvin, Luigi Titomanlio, Kumaran Deiva, Lea Lenglart
INDIAN JOURNAL OF PEDIATRICS
(2023)
Review
Clinical Neurology
Wesley T. Kerr, Stephane Auvin, Serge Van der Geyten, Christopher Kenney, Gerald Novak, Nathan B. Fountain, Caitlin Grzeskowiak, Jacqueline A. French
Summary: Well-designed placebo-controlled clinical trials are crucial for the development of new epilepsy treatments, but the design has remained unchanged for decades. Concerns have been raised by patients, clinicians, regulators, and innovators about the challenges of recruiting for trials, partly due to the static design of maintaining participants on add-on placebo for long periods of time when there are more therapy options available. Time-to-event trials, although having potential limitations, have been suggested as a promising mechanism to make trials more patient-friendly and reduce placebo exposure.
Article
Clinical Neurology
Stephane Auvin, Charlotte Nortvedt, Douglas S. Fuller, Farhad Sahebkar
Summary: This post hoc analysis evaluated the use of seizure-free days as a potential outcome measure in randomized placebo-controlled trials for patients with Lennox-Gastaut syndrome (LGS). The results showed that seizure-free days can be a meaningful and new endpoint for future trials in LGS patients.
Editorial Material
Clinical Neurology
Randi von Wrede, Juri-Alexander Witt, Stephane Auvin, Anita Devlin, Lieven Lagae, Anthony Marson, Kimford J. Meador, Terence J. O'Brien, Jun Park, Rainer Surges, Eugen Trinka, Samuel Wiebe, Christoph Helmstaedter
Article
Neurosciences
Walid Khrouf, Dario Saracino, Benoit Rucheton, Marion Houot, Fabienne Clot, Daisy Rinaldi, Joana Vitor, Marie Huynh, Evelyne Heng, Dimitri Schlemmer, Florence Pasquier, Vincent Deramecourt, Sophie Auriacombe, Carole Azuar, Richard Levy, Stephanie Bombois, Claire Boutoleau-Bretonniere, Jeremie Pariente, Mira Didic, David Wallon, Frederique Fluchere, Stephane Auvin, Imen Ben Younes, Yann Nadjar, Alexis Brice, Bruno Dubois, Dominique Bonnefont-Rousselot, Isabelle Le Ber, Foudil Lamari
Summary: GRN mutations lead to increased plasma levels of lysosphingolipids (lysoSPL) in individuals with frontotemporal dementia (FTD). Among FTD patients, lysoSPL levels are specifically elevated in GRN carriers. LGL1 levels are associated with neurofilament increases in presymptomatic carriers.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Clinical Neurology
S. Auvin, S. Baulac
Summary: Dysregulation of the mTOR pathway has been well studied in various neurodevelopmental disorders associated with epilepsy. Mutations in mTOR pathway genes play a role in tuberous sclerosis complex and different cortical malformations, leading to the concept of mTORopathies. This suggests that mTOR inhibitors could be used as antiseizure medication.
REVUE NEUROLOGIQUE
(2023)
Article
Clinical Neurology
Claudio Liguori, Estevo Santamarina, Adam Strzelczyk, Juan Jesus Rodriguez-Uranga, Rohit Shankar, Xiana Rodriguez-Osorio, Stephane Auvin, Paolo Bonanni, Eugen Trinka, Rob McMurray, Ricardo Sainz-Fuertes, Vicente Villanueva
Summary: The PERMIT study is the largest analysis of perampanel clinical practice data. The results showed that early add-on therapy with perampanel was more effective and better tolerated compared to late add-on therapy.
FRONTIERS IN NEUROLOGY
(2023)
Letter
Clinical Neurology
Aristea S. Galanopoulou, Stephane Auvin, Solomon L. Moshe, Heidrun Potschka, Luisa Rocha, Matthew C. Walker
Article
Clinical Neurology
Ronit M. Pressler, Nicholas S. Abend, Stephan Auvin, Geraldine Boylan, Francesco Brigo, Maria Roberta Cilio, Linda S. De Vries, Maurizio Elia, Alberto Espeche, Cecil D. Hahn, Terrie Inder, Nathalie Jette, Angelina Kakooza-Mwesige, Silke Mader, Eli M. Mizrahi, Solomon L. Moshe, Lakshmi Nagarajan, Iris Noyman, Magda L. Nunes, Pauline Samia, Eilon Shany, Renee A. Shellhaas, Ann Subota, Chahnez Charfi Triki, Tammy Tsuchida, Kollencheri Puthenveettil Vinayan, Jo M. Wilmshurst, Elissa G. Yozawitz, Hans Hartmann
Summary: Seizures in neonates are common, and the management of neonatal seizures varies significantly. The Neonatal Task Force of the International League Against Epilepsy has developed evidence-based recommendations for the management of antiseizure medication in neonates. These recommendations cover the choice of first-line and second-line medications, control of seizure burden, the use of therapeutic hypothermia, and other considerations.
Article
Clinical Neurology
Stephane Auvin, Aristea S. Galanopoulou, Solomon L. Moshe, Heidrun Potschka, Luisa Rocha, Matthew C. Walker
Summary: Despite progress in the development of anti-seizure medications (ASMs), one third of people with epilepsy have drug-resistant epilepsy (DRE). The working definition of DRE, proposed by the International League Against Epilepsy (ILAE) in 2010, helped identify individuals who might benefit from presurgical evaluation early on. There is a need to revisit the current definition of DRE in order to improve research, develop new treatments, and identify drug resistance earlier.
Article
Clinical Neurology
Nicola Specchio, Rima Nabbout, Eleonora Aronica, Stephane Auvin, Arianna Benvenuto, Luca de Palma, Martha Feucht, Floor Jansen, Katarzyna Kotulska, Harvey Sarnat, Lieven Lagae, Sergiusz Jozwiak, Paolo Curatolo
Summary: Children with tuberous sclerosis complex (TSC) often experience drug-resistant epilepsy, and significant progress has been made in understanding the mechanisms and management of TSC-associated epilepsy. Pre-symptomatic treatment with vigabatrin can delay seizure onset, while mTOR inhibition with everolimus and cannabidiol provide additional therapeutic options. Epilepsy surgery has shown to greatly improve seizure outcomes. Early identification of risk factors and genetic diagnosis, as well as the use of biomarkers, can contribute to the development of pre-symptomatic and disease-modifying strategies.
EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY
(2023)
Article
Clinical Neurology
Soufiane Mortaji, Blandine Dozieres-Puyravel, Katia Geraldes, Celine Perrot, Virginie Quemener, Stephane Auvin
Summary: This article reports two cases of patients who were not following any particular diet and experienced infrequent paroxysmal non-epileptic events. Intermittent glucose intake before physical activity and at the onset of symptoms consistently improved the symptoms. The observations suggest the possibility of developing a new treatment strategy involving sustained increase in blood glucose. However, this strategy should currently be limited to a small group of GLUT1-DS patients not on a ketogenic diet.
EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY
(2023)
Meeting Abstract
Clinical Neurology
Kim Bishop, Peter Isquith, Kelly Knupp, Joseph Sullivan, Rima Nabbout, Antonio Gil-Nagel, Ingrid Scheffer, Stephane Auvin, J. Helen Cross, Renzo Guerrini, Robert Roth, Gerard Gioia, Amelie Lothe, Shikha Polega