Article
Genetics & Heredity
Ana Ricobaraza, Maria Bunuales, Manuela Gonzalez-Aparicio, Saja Fadila, Moran Rubinstein, Irene Vides-Urrestarazu, Julliana Banderas, Noemi Sola-Sevilla, Rocio Sanchez-Carpintero, Jose Luis Lanciego, Elvira Roda, Adriana Honrubia, Patricia Arnaiz, Ruben Hernandez-Alcoceba
Summary: This study evaluated different approaches to achieve selective expression of the SCN1A gene in inhibitory neurons and developed a new gene vector that showed improved survival and amelioration of epileptic phenotype in a Dravet syndrome (DS) mouse model.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2023)
Review
Clinical Neurology
Lieven Lagae
Summary: Dravet syndrome is a refractory epilepsy syndrome with challenges in understanding the correlation between genetic mutations and clinical characteristics. Recent comprehensive guidelines and clinical studies have shown the positive effects of new drugs on cognition and quality of life.
CURRENT OPINION IN NEUROLOGY
(2021)
Article
Clinical Neurology
Wenhui Li, Amy L. Schneider, Ingrid E. Scheffer
Summary: An evidence-based definition of SCN1A-Dravet syndrome is crucial for early diagnosis. The study refines the spectrum of Dravet syndrome based on seizure onset patterns, types, and progression, highlighting the importance of understanding the full spectrum of SCN1A-Dravet syndrome presentation for early diagnosis and treatment optimization as precision medicine trials emerge.
Article
Neurosciences
Nina Miljanovic, Stefanie M. Hauck, R. Maarten van Dijk, Valentina Di Liberto, Ali Rezaei, Heidrun Potschka
Summary: The study utilized a mouse model of Dravet syndrome for proteomic analysis, revealing complex molecular alterations in the hippocampus during disease progression, involving neurotransmitter dynamics, ion channel function, and more. These findings provide valuable insights for the future development of therapeutic approaches.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Clinical Neurology
Nina Miljanovic, Roelof Maarten van Dijk, Verena Buchecker, Heidrun Potschka
Summary: Metabolic alterations in a Dravet mouse model were analyzed using untargeted metabolomics, showing changes in energy metabolism and impact on the glutamate/GABA-glutamine cycle. In addition, reductions in hippocampal levels of noradrenaline, corticosterone, and two bile acids were observed.
Article
Biotechnology & Applied Microbiology
Annie Tanenhaus, Timothy Stowe, Andrew Young, John McLaughlin, Rangoli Aeran, I. Winnie Lin, Jianmin Li, Raghavendra Hosur, Ming Chen, Jennifer Leedy, Tiffany Chou, Sirika Pillay, Maria Candida Vila, Jennifer A. Kearney, Martin Moorhead, Archana Belle, Stephanie Tagliatela
Summary: This study tested a gene therapy targeting SCN1A gene to treat Dravet syndrome. By upregulating SCN1A expression in inhibitory neurons, the therapy corrected the genetic defect and significantly reduced seizure occurrence, extending the lifespan of mice with the syndrome.
HUMAN GENE THERAPY
(2022)
Review
Pharmacology & Pharmacy
Kenneth A. A. Myers
Summary: Dravet syndrome is a severe epileptic encephalopathy in infants, mainly caused by mutations in SCN1A. Current treatments mainly focus on reducing seizure frequency, but have limited impact on co-morbidities. However, gene therapies targeting Na(V)1.1 show promising results in preclinical studies.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2023)
Article
Biology
Joanna Mattis, Ala Somarowthu, Kevin M. Goff, Evan Jiang, Jina Yom, Nathaniel Sotuyo, Laura M. Mcgarry, Huijie Feng, Keisuke Kaneko, Ethan M. Goldberg
Summary: Dravet syndrome is a neurodevelopmental disorder characterized by treatment-resistant epilepsy, intellectual disability, and increased risk of sudden death. A study found that there is a dysfunction in the filtering of input signals in the hippocampal dentate gyrus in a mouse model of Dravet syndrome. This dysfunction is not due to impaired inhibitory neurons, but rather excessive excitation to granule cells. Stimulation of certain neurons or inhibiting inhibitory neurons can lower the seizure threshold in these mice. Activation of inhibitory neurons can normalize the neuronal responses.
Article
Clinical Neurology
Helena Martins Custodio, Lisa M. Clayton, Ravishankara Bellampalli, Susanna Pagni, Katri Silvennoinen, Richard Caswell, John C. Ambrose, Andreas Brunklaus, Renzo Guerrini, Bobby P. C. Koeleman, Johannes R. Lemke, Rikke S. Moler, Ingrid E. Scheffer, Sarah Weckhuysen, Federico Zara, Sameer Zuberi, Karoline Kuchenbaecker, Simona Balestrini, James D. Mills, Sanjay M. Sisodiya
Summary: Dravet syndrome, a rare severe epilepsy caused by SCN1A variants, shows phenotypic heterogeneity that cannot be fully explained by the causal variant or clinical factors. In this study, additional genomic variation and rare variants in epilepsy-related genes were found to contribute to the phenotypic diversity of adults with SCN1A-related Dravet syndrome. The study also revealed differences in polygenic risk scores for intelligence and longevity between Dravet syndrome and epilepsy controls, suggesting that genetic background plays a role in the syndrome's phenotype and mortality risk.
Review
Clinical Neurology
Jiangwei Ding, Lei Wang, Zhe Jin, Yuanyuan Qiang, Wenchao Li, Yangyang Wang, Changliang Zhu, Shucai Jiang, Lifei Xiao, Xiaoyan Hao, Xulei Hu, Xinxiao Li, Feng Wang, Tao Sun
Summary: This study aimed to identify genes other than SCN1A that may cause DS or DS-like phenotypes. A comprehensive search of relevant studies was conducted, and a total of 29 studies met the inclusion criteria. The results suggest that various genes including PCDH19, SCN2A, SCN8A, SCN1B, GABRA1, GABRB3, GABRG2, KCNA2, CHD2, CPLX1, HCN1A, and STXBP1 may be involved in DS or DS-like phenotypes.
FRONTIERS IN NEUROLOGY
(2022)
Review
Clinical Neurology
Lori L. Isom, Kelly G. Knupp
Summary: Dravet syndrome is a severe developmental and epileptic encephalopathy associated with SCN1A variants. Despite new anti-seizure treatment options, achieving seizure freedom remains difficult. Precision medicine offers hope for DS patients with various potential treatments, but understanding patient selection, treatment impact assessment, and long-term risks are important considerations.
Article
Clinical Neurology
Elaine C. Wirrell, Veronica Hood, Kelly G. Knupp, Mary Anne Meskis, Rima Nabbout, Ingrid E. Scheffer, Jo Wilmshurst, Joseph Sullivan
Summary: This study aimed to reach a consensus on the diagnosis and management of Dravet syndrome (DS) by consulting experienced physicians and caregivers. The study summarized the current literature and obtained opinions from an expert panel on the diagnosis and management of DS. The results showed that there was consensus on the diagnosis and treatment of DS, but there was disagreement on disease-modifying therapies.
Article
Neurosciences
Matteo Lenge, Simona Balestrini, Davide Mei, Letizia Macconi, Maria Eugenia Caligiuri, Valeria Cuccarini, Domenico Aquino, Federica Mazzi, Ludovico d'Incerti, Francesca Darra, Bernardo Dalla Bernardina, Renzo Guerrini
Summary: Mutations of the SCN1A gene can cause epilepsy with various phenotypes, including Dravet syndrome. This study used neuroimaging methods to identify structural changes in the brains of 34 patients with SCN1A-related epilepsy. The findings showed bilateral atrophic changes in the hippocampus, amygdala, and temporo-limbic cortex, with the hippocampal formation as the epicenter of these changes. Dravet syndrome was associated with more severe atrophy patterns compared to genetic epilepsy with febrile seizures plus phenotype.
Article
Cell Biology
Wout J. Weuring, Jos W. Hoekman, Kees P. J. Braun, Bobby P. C. Koeleman
Summary: Genetic and functional differences between zebrafish strains used as models for Dravet Syndrome may impact their validity as reliable models.
Article
Neurosciences
Nikhil Sahai, Angela M. Bard, Orrin Devinsky, Franck Kalume
Summary: The study revealed that in response to mild heat stress, DS mice displayed significantly blunted correction of body temperature, with less suppression of heart rate and respiration rate compared to WT mice. During exercise stress, DS mice showed a diminished increase in heart rate, followed by an exaggerated HR suppression and HRV elevation during recovery, indicating the presence of autonomic disturbances in DS mice.
NEUROBIOLOGY OF DISEASE
(2021)
Editorial Material
Clinical Neurology
Sameer M. Zuberi
DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY
(2022)
Article
Clinical Neurology
Edouard Hirsch, Jacqueline French, Ingrid E. Scheffer, Alicia Bogacz, Taoufik Alsaadi, Michael R. Sperling, Fatema Abdulla, Sameer M. Zuberi, Eugen Trinka, Nicola Specchio, Ernest Somerville, Pauline Samia, Kate Riney, Rima Nabbout, Satish Jain, Jo M. Wilmshurst, Stephane Auvin, Samuel Wiebe, Emilio Perucca, Solomon L. Moshe, Paolo Tinuper, Elaine C. Wirrell
Summary: This paper aims to define the four syndromes comprising the idiopathic generalized epilepsies (IGEs) and provides updated diagnostic criteria. For patients who do not meet the criteria for these syndromes but have generalized seizure types, a classification is also provided. Recognizing these syndromes as a special grouping helps determine prognosis and treatment implications.
Article
Clinical Neurology
Sameer M. Zuberi, Elaine Wirrell, Elissa Yozawitz, Jo M. Wilmshurst, Nicola Specchio, Kate Riney, Ronit Pressler, Stephane Auvin, Pauline Samia, Edouard Hirsch, Santiago Galicchio, Chahnez Triki, O. Carter Snead, Samuel Wiebe, J. Helen Cross, Paolo Tinuper, Ingrid E. Scheffer, Emilio Perucca, Solomon L. Moshe, Rima Nabbout
Summary: This article proposes a classification and definition of epilepsy syndromes in neonates and infants, aiming to support epilepsy diagnosis and emphasize the importance of classifying epilepsy by syndrome and etiology. The article reports the epidemiology, clinical course, seizure types, EEG, neuroimaging, genetics, and differential diagnosis for each syndrome, and presents self-limited syndromes, developmental and epileptic encephalopathies, and etiology-specific epilepsy syndromes.
Article
Clinical Neurology
Nicola Specchio, Elaine C. Wirrell, Ingrid E. Scheffer, Rima Nabbout, Kate Riney, Pauline Samia, Marilisa Guerreiro, Sam Gwer, Sameer M. Zuberi, Jo M. Wilmshurst, Elissa Yozawitz, Ronit Pressler, Edouard Hirsch, Sam Wiebe, Helen J. Cross, Emilio Perucca, Solomon L. Moshe, Paolo Tinuper, Stephane Auvin
Summary: The 2017 International League Against Epilepsy classification defines a three-tier system for epilepsy syndromes, with childhood onset epilepsy syndromes falling into three categories: self-limited focal epilepsies, generalized epilepsies, and developmental and/or epileptic encephalopathies. Identification of specific syndromes helps guide management and prognosis. This paper describes these childhood onset epilepsy syndromes, highlighting their seizure types, EEG features, phenotypic variations, and key investigation findings.
Article
Clinical Neurology
Elaine C. Wirrell, Rima Nabbout, Ingrid E. Scheffer, Taoufik Alsaadi, Alicia Bogacz, Jacqueline A. French, Edouard Hirsch, Satish Jain, Sunao Kaneko, Kate Riney, Pauline Samia, O. Carter Snead, Ernest Somerville, Nicola Specchio, Eugen Trinka, Sameer M. Zuberi, Simona Balestrini, Samuel Wiebe, J. Helen Cross, Emilio Perucca, Solomon L. Moshe, Paolo Tinuper
Summary: This paper describes the process of reaching consensus on the classification and definition of epilepsy syndromes by the International League Against Epilepsy (ILAE), as well as providing clinical data templates for each syndrome. The diagnosis of an epilepsy syndrome carries significant implications for prognosis and treatment, and these syndromes often present with age-dependent characteristics and comorbidities.
Article
Clinical Neurology
Kate Riney, Alicia Bogacz, Ernest Somerville, Edouard Hirsch, Rima Nabbout, Ingrid E. Scheffer, Sameer M. Zuberi, Taoufik Alsaadi, Satish Jain, Jacqueline French, Nicola Specchio, Eugen Trinka, Samuel Wiebe, Stephane Auvin, Leonor Cabral-Lim, Ansuya Naidoo, Emilio Perucca, Solomon L. Moshe, Elaine C. Wirrell, Paolo Tinuper
Summary: The goal of this paper is to provide updated diagnostic criteria for epilepsy syndromes with variable age of onset, based on expert consensus. The aim is to aid diagnosis and guide investigations for etiology and treatments for these patients, incorporating advances in genetics, electroencephalography, and imaging.
Review
Behavioral Sciences
Joseph Sullivan, Alison M. Deighton, Maria Candida Vila, Shelagh M. Szabo, Benit Maru, Jacqueline S. Gofshteyn, Emma S. James, Salvador Rico, Sameer M. Zuberi
Summary: Dravet syndrome is a developmental and epileptic encephalopathy characterized by a changing disease course as individuals age. There is a lack of comprehensive systematic review of the contemporary literature on DS, but available evidence indicates that it is not limited to seizures; non-seizure manifestations appear early in life and increase over time, significantly contributing to the burden of the disease on individuals, families, and healthcare systems. The HRQoL in DS is primarily affected by seizure severity, cognition, and motor and behavioral problems.
EPILEPSY & BEHAVIOR
(2022)
Article
Clinical Neurology
Kelly G. Knupp, Ingrid E. Scheffer, Berten Ceulemans, Joseph E. Sullivan, Katherine C. Nickels, Lieven Lagae, Renzo Guerrini, Sameer M. Zuberi, Rima Nabbout, Kate Riney, Svetlana Shore, Anupam Agarwal, Michael Lock, Gail M. Farfel, Bradley S. Galer, Arnold R. Gammaitoni, Ronald Davis, Antonio Gil-Nagel
Summary: The trial demonstrates the efficacy of fenfluramine in reducing drop seizures in patients with Lennox-Gastaut syndrome (LGS) and suggests that it may be particularly beneficial for those experiencing generalized tonic-clonic seizures.
Article
Clinical Neurology
Andreas Brunklaus, Tobias Bruenger, Tony Feng, Carmen Fons, Anni Lehikoinen, Eleni Panagiotakaki, Mihaela-Adela Vintan, Joseph Symonds, James Andrew, Alexis Arzimanoglou, Sarah Delima, Julie Gallois, Donncha Hanrahan, Gaetan Lesca, Stewart MacLeod, Dragan Marjanovic, Amy McTague, Noemi Nunez-Enamorado, Eduardo Perez-Palma, M. Scott Perry, Karen Pysden, Sophie J. Russ-Hall, Ingrid E. Scheffer, Krystal Sully, Steffen Syrbe, Ulvi Vaher, Murugan Velayutham, Julie Vogt, Shelly Weiss, Elaine Wirrell, Sameer M. Zuberi, Dennis Lal, Rikke S. Moller, Massimo Mantegazza, Sandrine Cestele
Summary: This study describes different phenotypes of SCN1A-related epilepsy, some of which are associated with febrile seizures and familial hemiplegic migraine. The research found that these phenotypes are caused by SCN1A variants, and by conducting clinical, genetic, and functional evaluations of the affected individuals, it reveals the potential efficacy of sodium channel blockers in treating this disease.
Article
Clinical Neurology
Ronny Wickstrom, Olga Taraschenko, Robertino Dilena, Eric T. Payne, Nicola Specchio, Rima Nabbout, Sookyong Koh, Nicolas Gaspard, Lawrence J. Hirsch
Summary: This study aims to develop consensus-based recommendations for the management of adult and pediatric patients with new-onset refractory status epilepticus (NORSE)/febrile infection-related epilepsy syndrome (FIRES) based on best available evidence and expert opinion. The Delphi methodology was used to gather opinions from 48 experts, resulting in consensus recommendations covering disease characteristics, diagnosis, treatment, and research directions.
Article
Clinical Neurology
Tobias Brunger, Eduardo Perez-Palma, Ludovica Montanucci, Michael Nothnagel, Rikke S. Moller, Stephanie Schorge, Sameer Zuberi, Joseph Symonds, Johannes R. Lemke, Andreas Brunklaus, Stephen F. Traynelis, Patrick May, Dennis Lal
Summary: This study aimed to systematically identify biological features associated with variant pathogenicity in ion-channel genes and found that these features are correlated with clinical phenotypes and molecular measurements in patients with neurodevelopmental disorders. The results suggest the feasibility of clinical decision support algorithms that can predict variant pathogenicity and function in the future.
Article
Clinical Neurology
Kelly G. Knupp, Ingrid E. Scheffer, Berten Ceulemans, Joseph Sullivan, Katherine C. Nickels, Lieven Lagae, Renzo Guerrini, Sameer M. Zuberi, Rima Nabbout, Kate Riney, Anupam Agarwal, Michael Lock, David Dai, Gail M. Farfel, Bradley S. Galer, Arnold R. Gammaitoni, Shikha Polega, Ronald Davis, Antonio Gil-Nagel
Summary: Long-term use of fenfluramine showed sustained reduction in drop seizure frequency in LGS patients, with significant reduction in the frequency of GTCS and tonic seizures. The drug was generally well tolerated with minimal adverse effects and no significant cardiac side effects observed. Fenfluramine may serve as an important long-term treatment option for patients with LGS.
Article
Clinical Neurology
Phoebe Makiello, Tony Feng, Benjamin Dunwoody, Felix Steckler, Joseph Symonds, Sameer M. Zuberi, Liam Dorris, Andreas Brunklaus
Summary: This study investigated long-term predictors of health-related quality of life (HRQOL) in patients with Dravet syndrome (DS) and found that younger patients showed a significant decline in HRQOL and the use of sodium channel blockers negatively impacted long-term HRQOL.
Article
Clinical Neurology
Elissa G. Yozawitz, Maria R. Cilio, Eli M. Mizrahi, Jee-Young Moon, Solomon L. Moshe, Magda L. Nunes, Perrine Plouin, Sampsa Vanhatalo, Sameer Zuberi, Ronit M. Pressler
Summary: The ILAE Neonatal Seizure Framework was tested and found to be a better classification system for clinical seizures. Among all seizure types, clonic seizures were the easiest to identify accurately.
EPILEPTIC DISORDERS
(2023)
Review
Genetics & Heredity
Adam Strzelczyk, Sameer M. M. Zuberi, Pasquale Striano, Felix Rosenow, Susanne Schubert-Bast
Summary: This study conducted a systematic literature review on the burden of illness in Lennox-Gastaut syndrome (LGS), finding that LGS patients suffer from drug-resistant epilepsy and cognitive dysfunction. The research on the epidemiology, treatment costs, and patient quality of life in LGS is limited, indicating a need for further investigation.
ORPHANET JOURNAL OF RARE DISEASES
(2023)