4.6 Editorial Material

Advances in epilepsy shed light on key questions

Journal

NATURE REVIEWS NEUROLOGY
Volume 9, Issue 2, Pages 66-68

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/nrneurol.2012.272

Keywords

-

Ask authors/readers for more resources

Research on epilepsies in 2012 has substantially advanced our knowledge of these often devastating conditions. From important discoveries that revealed causative factors and the molecular basis of disease, to major implications for surgical decision-making, these studies set the scene for future advances in the field. Scheffer, I. E. & Mullen, S. A. Nat. Rev. Neurol. 9, 66-68 (2013); published online 8 January 2013; doi:10.1038/nrneurolt.2012.272

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Article Biochemistry & Molecular Biology

Comparing saliva and blood for the detection of mosaic genomic abnormalities that cause syndromic intellectual disability

David I. Francis, Zornitza Stark, Ingrid E. Scheffer, Tiong Yang Tan, Krithika Murali, Lyndon Gallacher, David J. Amor, Himanshu Goel, Lilian Downie, Chloe A. Stutterd, Emma I. Krzesinski, Anand Vasudevan, Ralph Oertel, Vida Petrovic, Amber Boys, Vivian Wei, Trent Burgess, Karen Dun, Karen L. Oliver, Anne Baxter, Anna Hackett, Samantha Ayres, Sebastian Lunke, Paul Kalitsis, Meaghan Wall

Summary: This study aimed to compare the diagnostic yield of saliva and blood for pathogenic copy number variants (CNVs). The results showed that saliva microarray testing had increased diagnostic utility over blood testing in individuals with syndromic intellectual disability (ID). Mosaic pathogenic CNVs or aneuploidy were detected in saliva but not in blood.

EUROPEAN JOURNAL OF HUMAN GENETICS (2023)

Correction Biochemistry & Molecular Biology

Genetic aetiologies for childhood speech disorder: novel pathways co-expressed during brain development(jan, 10.1038/s41380022-01764-8, 2023)

Antony Kaspi, Michael S. Hildebrand, Victoria E. Jackson, Ruth Braden, Olivia van Reyk, Tegan Howell, Simone Debono, Mariana Lauretta, Lottie Morison, Matthew J. Coleman, Richard Webster, David Coman, Himanshu Goel, Mathew Wallis, Gabriel Dabscheck, Lilian Downie, Emma K. Baker, Bronwyn Parry-Fielder, Kirrie Ballard, Eva Harrold, Shaun Ziegenfusz, Mark F. Bennett, Erandee Robertson, Longfei Wang, Amber Boys, Simon E. Fisher, David J. Amor, Ingrid E. Scheffer, Melanie Bahlo, Angela T. Morgan

MOLECULAR PSYCHIATRY (2023)

Article Clinical Neurology

Epidemiology of Developmental and Epileptic Encephalopathy and of Intellectual Disability and Epilepsy in Children

Gemma Poke, James Stanley, Ingrid E. Scheffer, Lynette G. Sadleir

Summary: The study aimed to determine the population-based cumulative incidence and prevalence of developmental and epileptic encephalopathies (DEEs) and intellectual disability and epilepsy (ID+E) in children. The findings showed that 1 in 340 children under the age of 16 has epilepsy and developmental impairment, with 1 in 590 having a DEE and 1 in 800 having ID+E.

NEUROLOGY (2023)

Article Genetics & Heredity

Australian Genomics: Outcomes of a 5-year national program to accelerate the integration of genomics in healthcare

Zornitza Stark, Tiffany Boughtwood, Matilda Haas, Jeffrey Braithwaite, Clara L. Gaff, Ilias Goranitis, Amanda B. Spurdle, David P. Hansen, Oliver Hofmann, Nigel Laing, Sylvia Metcalfe, Ainsley J. Newson, Hamish S. Scott, Natalie Thorne, Robyn L. Ward, Marcel E. Dinger, Stephanie Best, Janet C. Long, Sean M. Grimmond, John Pearson, Nicola Waddell, Christopher P. Barnett, Matthew Cook, Michael Field, David Fielding, Stephen B. Fox, Jozef Gecz, Adam Jaffe, Richard J. Leventer, Paul J. Lockhart, Sebastian Lunke, Andrew J. Mallett, Julie McGaughran, Linda Mileshkin, Katia Nones, Tony Roscioli, Ingrid E. Scheffer, Christopher Semsarian, Cas Simons, David M. Thomas, David R. Thorburn, Richard Tothill, Deborah White, Sally Dunwoodie, Peter T. Simpson, Peta Phillips, Marie-Jo Brion, Keri Finlay, Michael CJ. Quinn, Tessa Mattiske, Emma Tudini, Kirsten Boggs, Sean Murray, Kathy Wells, John Cannings, Andrew H. Sinclair, John Christodoulou, Kathryn N. North

Summary: Australian Genomics is a national collaborative partnership that aims to integrate genomics into healthcare through a whole-of-system approach. It has evaluated genomic testing outcomes in over 5,200 individuals across rare disease and cancer studies and provided evidence-based changes in policy and practice, resulting in government funding and access to genomic tests. It has also developed national skills, infrastructure, policy, and data resources to support data sharing and improve clinical genomic delivery.

AMERICAN JOURNAL OF HUMAN GENETICS (2023)

Article Clinical Neurology

Widespread genomic influences on phenotype in Dravet syndrome, a 'monogenic' condition

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.

BRAIN (2023)

Article Clinical Neurology

Indications and prescribing patterns of antiseizure medications in children in New Zealand

Shayma Ali, James Stanley, Suzanne Davis, Ngaire Keenan, Ingrid E. Scheffer, Lynette G. Sadleir

Summary: This retrospective study aimed to determine the indications and prescribing patterns for antiseizure medications (ASMs) in children in New Zealand. The results showed that the majority of children were prescribed ASMs for seizures, while smaller proportions were prescribed for pain, headache, mental health, and movement disorders. The study also revealed differences in prescribing patterns based on age, sex, and socioeconomic status, highlighting the need for tailored messaging and health policies to improve equity of epilepsy care.

DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY (2023)

Article Clinical Neurology

Recognition and epileptology of protracted CLN3 disease

Jillian M. Cameron, John A. Damiano, Bronwyn Grinton, Patrick W. Carney, Penny McKelvie, Peter Silbert, Nicholas Lawn, Ingrid E. Scheffer, Karen L. Oliver, Michael S. Hildebrand, Samuel F. Berkovic

Summary: This study analyzed the phenotypic features of a group of patients with protracted CLN3 disease in order to improve recognition of the disorder. The results showed that visual impairment was the initial symptom, with onset at 5-9 years, similar to classic CLN3 disease. The disease is often accompanied by progressive generalized and focal seizures.

EPILEPSIA (2023)

Editorial Material Clinical Neurology

The fascinating phenotypic spectrum of SCN1A gain-of-function epilepsies

Ingrid E. Scheffer

EPILEPSIA (2023)

Article Clinical Neurology

Contribution of Somatic Ras/Raf/Mitogen-Activated Protein Kinase Variants in the Hippocampus in Drug-Resistant Mesial Temporal Lobe Epilepsy

Sattar Khoshkhoo, Yilan Wang, Yasmine Chahine, E. Zeynep Erson-Omay, Stephanie M. Robert, Emre Kiziltug, Eyiyemisi C. Damisah, Carol Nelson-Williams, Guangya Zhu, Wenna Kong, August Yue Huang, Edward Stronge, H. Westley Phillips, Brian H. Chhouk, Sara Bizzotto, Ming Hui Chen, Thiuni N. Adikari, Zimeng Ye, Tom Witkowski, Dulcie Lai, Nadine Lee, Julie Lokan, Ingrid E. Scheffer, Samuel F. Berkovic, Shozeb Haider, Michael S. Hildebrand, Edward Yang, Murat Gunel, Richard P. Lifton, R. Mark Richardson, Ingmar Bluemcke, Sanda Alexandrescu, Anita Huttner, Erin L. Heinzen, Jidong Zhu, Annapurna Poduri, Nihal DeLanerolle, Dennis D. Spencer, Eunjung Alice Lee, Christopher A. Walsh, Kristopher T. Kahle

Summary: This study found pathogenic somatic variants in the hippocampus of patients with drug-resistant temporal lobe epilepsy, suggesting their association with the disease pathogenesis. These findings offer new insights into the genetic mechanisms and potential therapeutic targets for this common type of epilepsy.

JAMA NEUROLOGY (2023)

Article Clinical Neurology

Fenfluramine in the treatment of Dravet syndrome: Results of a third randomized, placebo-controlled clinical trial

Joseph Sullivan, Lieven Lagae, J. Helen Cross, Orrin Devinsky, Renzo G. Guerrini, Kelly Knupp, Linda Laux, Marina Nikanorova, Tilman Polster, Dinesh Talwar, Berten Ceulemans, Rima M. Nabbout, Gail S. Farfel, Bradley R. Galer, Arnold Gammaitoni, Michael Lock, Anupam E. Agarwal, Ingrid Scheffer, FAiRE DS Study Grp

Summary: This study examined the safety and effectiveness of fenfluramine in treating convulsive seizures in patients with Dravet syndrome. The results showed that patients treated with fenfluramine had lower seizure frequency and longer interval between seizures compared to the placebo group. Common side effects of fenfluramine were observed, but no evidence of severe cardiac or vascular issues was found.

EPILEPSIA (2023)

Editorial Material Clinical Neurology

Are Germline Mosaic TSC1/2 Variants Present in Controls? Implications for Diagnosis

Zimeng Ye, Sufang Lin, Xia Zhao, Mathew Wallis, Xinyi Gao, Li Sun, Jiarui Wu, Jing Duan, Yi Yao, Lin Li, Li Chen, Dezhi Cao, Zhanqi Hu, Victor W. Zhang, Samuel F. Berkovic, Ingrid E. Scheffer, Jianxiang Liao, Michael S. Hildebrand

PEDIATRIC NEUROLOGY (2024)

Article Cell & Tissue Engineering

Generation of an iPSC line (FINi001-A) from a girl with developmental and epileptic encephalopathy due to a heterozygous gain-of-function p.R1882Q variant in the voltage-gated sodium channel Nav1.2 protein encoded by the SCN2A gene

D. A. Ovchinnikov, S. Jong, C. Cuddy, I. E. Scheffer, S. Maljevic, S. Petrou

Summary: We generated an iPSC cell line from the fibroblasts of a girl with early infantile DEE carrying a gain-of-function mutation in Nav1.2 protein. The established iPSC line exhibited typical characteristics of human pluripotent stem cells and can be used to develop stem cell-based DEE models, contributing to the understanding and potential therapy development for this debilitating condition.

STEM CELL RESEARCH (2023)

Article Multidisciplinary Sciences

Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals

Ludovica Montanucci, David Lewis-Smith, Ryan L. Collins, Lisa-Marie Niestroj, Shridhar Parthasarathy, Julie Xian, Shiva Ganesan, Marie Macnee, Tobias Bruenger, Rhys H. Thomas, Michael Talkowski, Ingo Helbig, Costin Leu, Dennis Lal, Joshua E. Motelow, Gundula Povysil, Ryan S. Dhindsa, Kate E. Stanley, Andrew S. Allen, David B. Goldstein, Yen-Chen Anne Feng, Daniel P. Howrigan, Liam E. Abbott, Katherine Tashman, Felecia Cerrato, Caroline Cusick, Tarjinder Singh, Henrike Heyne, Andrea E. Byrnes, Claire Churchhouse, Nick Watts, Matthew Solomonson, Dennis Lal, Namrata Gupta, Benjamin M. Neale, Samuel F. Berkovic, Holger Lerche, David B. Goldstein, Daniel H. Lowenstein, Samuel F. Berkovic, Holger Lerche, David B. Goldstein, Daniel H. Lowenstein, Gianpiero L. Cavalleri, Patrick Cossette, Chris Cotsapas, Peter De Jonghe, Tracy Dixon-Salazar, Renzo Guerrini, Hakon Hakonarson, Erin L. Heinzen, Ryan S. Dhindsa, Kate E. Stanley, Ingo Helbig, Patrick Kwan, Anthony G. Marson, Slave Petrovski, Sitharthan Kamalakaran, Sanjay M. Sisodiya, Randy Stewart, Sarah Weckhuysen, Chantal Depondt, Dennis J. Dlugos, Ingrid E. Scheffer, Pasquale Striano, Catharine Freyer, Roland Krause, Patrick May, Kevin McKenna, Brigid M. Regan, Caitlin A. Bennett, Stephanie L. Leech, Costin Leu, David Lewis-Smith, Samuel F. Berkovic, Ingrid E. Scheffer, Brigid M. Regan, Caitlin A. Bennett, Stephanie L. Leech, Terence J. O'Brien, Slave Petrovski, Marian Todaro, Patrick Kwan, Sarah Weckhuysen, Peter De Jonghe, Hannah Stamberger, Chantal Depondti, Danielle M. Andrade, Quratulain Zulfiqar Ali, Tara R. Sadoway, Heinz Krestel, Andre Schaller, Savvas S. Papacostas, Ioanna Kousiappa, George A. Tanteles, Christou Yiolanda, Katalin Sterbova, Marketa Vlckova, Lucie Sedlackova, Petra Lassuthova, Karl Martin Klein, Felix Rosenow, Philipp S. Reif, Susanne Knake, Bernd A. Neubauer, Friedrich Zimprich, Martha Feucht, Eva Reinthaler, Wolfram S. Kunz, Gabor Zsurka, Rainer Surges, Tobias H. Baumgartner, Randi von Wrede, Ingo Helbig, Karl Martin Klein, Manuela Pendziwiat, Hiltrud Muhle, Annika Rademacher, Andreas van Baalen, Sarah von Spiczak, Ulrich Stephani, Zaid Afawi, Amos D. Korczyn, Moien Kanaan, Christina Canavati, Gerhard Kurlemann, Karen Mueller-Schlueter, Gerhard Kluger, Martin Haeusler, Ilan Blatt, Johannes R. Lemke, Ilona Krey, Holger Lerche, Yvonne G. Weber, Stefan Wolking, Felicitas Becker, Stephan Lauxmann, Christian Bosselmann, Josua Kegele, Christian Hengsbach, Sarah Rau, Bernhard J. Steinhoff, Andreas Schulze-Bonhage, Ingo Borggrafe, Christoph J. Schankin, Susanne Schubert-Bast, Herbert Schreiber, Thomas Mayer, Rudolf Korinthenberg, Knut Brockmann, Markus Wolff, Gerhard Kurlemann, Dieter Dennig, Rene Madeleyn, Josua Kegele, Reetta Kalviainen, Anni Saarela, Oskari Timonen, Tarja Linnankivi, Anna-Elina Lehesjoki, Sylvain Rheims, Gaetan Lesca, Philippe Ryvlin, Louis Maillard, Luc Valton, Philippe Derambure, Fabrice Bartolomei, Edouard Hirsch, Veronique Michel, Francine Chassoux, Mark I. Rees, Seo-Kyung Chung, William O. Pickrell, Robert H. W. Powell, Mark D. Baker, Beata Fonferko-Shadrach, Charlotte Lawthom, Joe Anderson, Sanjay M. Sisodiya, Natascha Schneider, Simona Balestrini, Sara Zagaglia, Vera Braatz, Anthony G. Marson, Michael R. Johnson, Pauls Auce, Graeme J. Sills, Patrick Kwan, Larry W. Baum, Pakc. Sham, Stacey S. Cherny, Colin H. T. Lui, Gianpiero L. Cavalleri, Norman Delanty, Colin P. Doherty, Arif Shukralla, Hany El-Naggar, Peter Widdess-Walsh, Nina Barisic, Laura Canafoglia, Silvana Franceschetti, Barbara Castellotti, Tiziana Granata, Francesca Ragona, Pasquale Striano, Federico Zara, Michele Iacomino, Antonella Riva, Francesca Madia, Maria Stella Vari, Vincenzo Salpietro, Marcello Scala, Maria Margherita Mancardi, Nobili Lino, Elisa Amadori, Thea Giacomini, Francesca Bisulli, Tommaso Pippucci, Laura Licchetta, Raffaella Minardi, Paolo Tinuper, Lorenzo Muccioli, Barbara Mostacci, Antonio Gambardella, Angelo Labate, Grazia Annesi, Lorella Manna, Monica Gagliardi, Renzo Guerrini, Elena Parrini, Davide Mei, Annalisa Vetro, Claudia Bianchini, Martino Montomoli, Viola Doccini, Carmen Barba, Shinichi Hirose, Atsushi Ishii, Toshimitsu Suzuki, Yushi Inoue, Kazuhiro Yamakawa, Ahmad Beydoun, Wassim Nasreddine, Nathalie Khoueiry-Zgheib, Birute Tumiene, Algirdas Utkus, Lynette G. Sadleir, Chontelle King, S. Hande Caglayan, Mutluay Arslan, Zuhal Yapici, Pinar Topaloglu, Bulent Kara, Uluc Yis, Dilsad Turkdogan, Asli Gundogdu-Eken, Nerses Bebek, Sibel Ugur-Iseri, Betul Baykan, Baris Salman, Garen Haryanyan, Emrah Yucesan, Yesim Kesim, Cigdem Ozkara, Meng-Han Tsai, Chen-Jui Ho, Chih-Hsiang Lin, Kuang-Lin Lin, I-Jun Chou, Annapurna Poduri, Beth R. Shiedley, Catherine Shain, Jeffrey L. Noebels, Alicia Goldman, Robyn M. Busch, Lara Jehi, Imad M. Najm, Dennis Lal, Lisa Ferguson, Jean Khoury, Tracy A. Glauser, Peggy O. Clark, Russell J. Buono, Thomas N. Ferraro, Michael R. Sperling, Dennis J. Dlugos, Warren Lo, Michael Privitera, Jacqueline A. French, Patrick Cossette, Steven Schachter, Hakon Hakonarson, Daniel H. Lowenstein, Ruben I. Kuzniecky, Dennis J. Dlugos, Orrin Devinsky, Daniel H. Lowenstein, Ruben I. Kuzniecky, Jacqueline A. French, Manu Hegde, David A. Greenberg, Ingo Helbig, Colin A. Ellis, Ethan Goldberg, Katherine L. Helbig, David Lewis-Smith, Mahgenn Cosico, Priya Vaidiswaran, Eryn Fitch, Charles R. J. C. Newton, SymonM. Kariuki, Ryan G. Wagner, Seth Owusu-Agyei, Andrew J. Cole, ChristopherM. McGraw, S. Anthony Siena, Lea Davis, Donald Hucks, Annika Faucon, David Wu, Bassel W. Abou-Khalil, Kevin Haas, Randip S. Taneja

Summary: In this study, the authors conducted a meta-analysis involving 26,699 individuals with seizure disorders and 492,324 population controls, and identified 25 genome-wide significant copy-number variants (CNVs). These findings provide new insights into the genetic risk factors for epilepsy and related seizure disorders, and may have implications for clinical practice.

NATURE COMMUNICATIONS (2023)

Article Clinical Neurology

Evaluation of the feasibility, diagnostic yield, and clinical utility of rapid genome sequencing in infantile epilepsy (Gene-STEPS): an international, multicentre, pilot cohort study

Alissa M. D'Gama, Sarah Mulhern, Beth R. Sheidley, Fadil Boodhoo, Sarah Buts, Natalie J. Chandler, Joanna Cobb, Meredith Curtis, Edwardj Higginbotham, Jonathon Holland, Tayyaba Khan, Julia Koh, Nicole S. Yliang, Lyndsey Mcrae, Sarah E. Nesbitt, Brandon T. Oby, Ben Paternoster, Alistair Patton, Graham Rose, Elizabeth Scotchman, Rozalia Valentine, Kimberly N. Wiltrout, Robin Z. Hayeems, Puneet Jain, Sebastian Lunke, Christian R. Marshall, Shira Rockowitz, Neilj Sebire, Zornitza Stark, Susan M. White, Lyn S. Chitty, J. Helen Cross, Ingrid E. Scheffer, Vann Chau, Gregory Costain, Annapurna Poduri, Katherine B. Howell, Amy McTague

Summary: A cohort study was conducted to determine the feasibility and clinical utility of rapid genome sequencing in infants with new-onset epilepsy. Among 100 infants enrolled in the study, genetic diagnoses were identified in 43% of the cases. Rapid genome sequencing had immediate clinical impact on treatment, evaluation, prognosis, and recurrence risk counselling.

LANCET NEUROLOGY (2023)

Article Clinical Neurology

Cation leak: a common functional defect causing HCN1 developmental and epileptic encephalopathy

Chaseley E. McKenzie, Ian C. Forster, Ming S. Soh, A. Marie Phillips, Lauren E. Bleakley, Sophie J. Russ-Hall, Kenneth A. Myers, Ingrid E. Scheffer, Christopher A. Reid

Summary: This study describes the functional analysis of seven pathogenic variants of HCN1 occurring in the transmembrane domain. A common cation leak characteristic was identified in all seven variants, suggesting that cation leak is an important pathogenic mechanism in HCN1 developmental and epileptic encephalopathy.

BRAIN COMMUNICATIONS (2023)

No Data Available