Article
Biochemistry & Molecular Biology
Ciria C. Hernandez, Yanwen Shen, Ningning Hu, Wangzhen Shen, Vinodh Narayanan, Keri Ramsey, Wen He, Liping Zou, Robert L. Macdonald
Summary: Febrile seizures (FS) are the most common form of epilepsy in children between six months and five years of age. Most of the variants associated with FS are found in the GABA(A) receptor gamma 2 subunit (GABRG2), leading to the loss of receptor function and negative impact on receptor biogenesis. Variants in GABRG2 result in a spectrum of phenotypic severity, ranging from asymptomatic to Dravet syndrome individuals, highlighting the relationship between the occurrence of variants and disease severity.
Article
Neurosciences
Yang Tian, Qiong-Xiang Zhai, Xiao-Jing Li, Zhen Shi, Chuan-Fang Cheng, Cui-Xia Fan, Bin Tang, Ying Zhang, Yun-Yan He, Wen-Bin Li, Sheng Luo, Chi Hou, Wen-Xiong Chen, Wei-Ping Liao, Jie Wang
Summary: This study identified ATP6V0C gene mutations associated with febrile seizures (FS) and epilepsy with febrile seizures plus (EFS+). These mutations may affect the protein function and lead to afebrile seizures. Screening for ATP6V0C mutations can differentiate patients from other related diseases such as Dravet syndrome.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Clinical Neurology
Sarah E. Heron, Brigid M. Regan, Rebekah V. Harris, Alison E. Gardner, Matthew J. Coleman, Mark F. Bennett, Bronwyn E. Grinton, Katherine L. Helbig, Michael R. Sperling, Sheryl Haut, Eric B. Geller, Peter Widdess-Walsh, James T. Pelekanos, Melanie Bahlo, Slave Petrovski, Erin L. Heinzen, Michael S. Hildebrand, Mark A. Corbett, Ingrid E. Scheffer, Jozef Gecz, Samuel F. Berkovic
Summary: Missense variants in SLC32A1 have been identified as causative for GEFS+ and IGE, leading to altered neuronal inhibition by affecting GABA transport. These findings have been validated by studying multiple families.
Article
Clinical Neurology
Mahmoud Koko, Joshua E. Motelow, Kate E. Stanley, Dheeraj R. Bobbili, Ryan S. Dhindsa, Patrick May
Summary: GABRG2 likely plays an important role in familial GGE, while the association of GABAergic signaling gene sets with familial GGE is more prominent than with sporadic GGE.
Article
Neurosciences
Jia Li, Si-Mei Lin, Jing-Da Qiao, Xiao-Rong Liu, Jie Wang, Mi Jiang, Jing Zhang, Min Zhong, Xu-Qin Chen, Jing Zhu, Na He, Tao Su, Yi-Wu Shi, Yong-Hong Yi, Wei-Ping Liao
Summary: This study identified CELSR3 gene variants potentially associated with FS/EFS+, leading to impaired protein function, but patients had favorable outcomes without neurodevelopmental disorders.
CNS NEUROSCIENCE & THERAPEUTICS
(2022)
Article
Neurosciences
Qi Zhang, Cynthia Forster-Gibson, Eduard Bercovici, Alexandra Bernardo, Fei Ding, Wangzhen Shen, Katherine Langer, Tonia Rex, Jing-Qiong Kang
Summary: This study is the first report of haploinsufficiency of two GABR epilepsy genes and visual impairment due to altered axonal myelination and resultant optic nerve atrophy. The study suggests the far-reaching impact of GABR mutations and the translational significance of animal models with the same etiology.
EXPERIMENTAL NEUROLOGY
(2023)
Article
Clinical Neurology
Maria Vlachou, Philippe Ryvlin, Anca Adriana Arbune, Sidsel Armand Larsen, Annette Skraep Sidaros, Melita Cacic Hribljan, Martin Fabricius, Sandor Beniczky
Summary: Postictal generalized EEG suppression (PGES) is a surrogate marker for sudden unexpected death in epilepsy (SUDEP), and the gradually increasing inhibitory phenomena may lead to prolonged PGES. GCS type 1 and progressive slowing of clonic phase (PSCP) have been identified as predictors for PGES, highlighting the importance of recognizing these ictal phenomena for risk assessment.
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
Ling Li, Lamei Yuan, Wen Zheng, Yan Yang, Xiong Deng, Zhi Song, Hao Deng
Summary: This study identified a disease-causing variant in a Chinese Tujia ethnic family with Genetic Epilepsy with Febrile Seizures Plus (GEFSP) using whole exome sequencing, Sanger sequencing, and in silico prediction. The variant in the sodium voltage-gated channel alpha subunit 1 gene (SCN1A) coding region was found to co-segregate with the GEFSP phenotype and was predicted as disease-causing. These findings expand the genetic and phenotypic spectrum of GEFSP and have implications for genetic diagnoses, personalized therapies, and prognoses.
FRONTIERS IN NEUROLOGY
(2023)
Article
Clinical Neurology
Hongxia Ma, Yuxiong Guo, Zhihong Chen, Lingan Wang, Zhihong Tang, Jingwen Zhang, Qinfei Miao, Qiongxiang Zhai
Summary: The study identified mutations in SCN1A, SCN3A, and SCN9A genes as potential causes of EFS+ in the Southern Chinese Han population. These mutations led to varied clinical phenotypes in patients, including febrile seizures, Dravet Syndrome, etc.
SEIZURE-EUROPEAN JOURNAL OF EPILEPSY
(2021)
Article
Clinical Neurology
Sarah E. Heron, Brigid M. Regan, Rebekah V. Harris, Alison E. Gardner, Matthew J. Coleman, Mark F. Bennett, Bronwyn E. Grinton, Katherine L. Helbig, Michael R. Sperling, Sheryl Haut, Eric B. Geller, Peter Widdess-Walsh, James T. Pelekanos, Melanie Bahlo, Slave Petrovski, Erin L. Heinzen, Michael S. Hildebrand, Mark A. Corbett, Ingrid E. Scheffer, Jozef Gecz, Samuel F. Berkovic
Summary: By sequencing genomes of family members, eight previously unreported missense variants in SLC32A1 were identified to cause genetic epilepsy, impacting GABA transport and neuronal inhibition. Further examination of epilepsy cohorts is needed to fully understand the genotype-phenotype spectrum associated with SLC32A1 variants.
Article
Pediatrics
Jian Ding, Chun Wang, Guo-Qiang Huang, Jing-Wen Zhang, Qiong-Xiang Zhai, Zhi-Hong Chen, Yu-Xin Zhang, Yu-Xiong Guo
Summary: This study found that the mutation of KCNAB3 gene could lead to a decrease in hippocampal potassium currents in a mouse model of GEFS+. This result helps to reveal the pathogenesis of GEFS+.
TRANSLATIONAL PEDIATRICS
(2022)
Article
Biochemistry & Molecular Biology
Alexandra V. Griflyuk, Tatyana Y. Postnikova, Sergey L. Malkin, Aleksey V. Zaitsev
Summary: Febrile seizures during early childhood can cause central nervous system developmental disorders. The specific mechanisms of how febrile seizures affect the developing brain are not well understood. In this study, we used a hyperthermic model of febrile seizures in 10-day-old rats and tracked their development for two months. Our findings suggest that febrile seizures reduce the number of neurons in various regions of the hippocampus and impair glutamatergic transmission, leading to decreased local field potential amplitude.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Omar Ashraf, Trong Huynh, Benton S. Purnell, Madhuvika Murugan, Denise E. Fedele, Vineet Chitravanshi, Detlev Boison
Summary: SUDEP, a leading cause of death in patients with refractory epilepsy, is believed to be caused by centrally-mediated respiratory dysfunction. Research shows that seizures can trigger a surge in adenosine release, which suppresses breathing. Suppressing phrenic nerve activity may serve as a predictive biomarker for imminent SUDEP, allowing for timely intervention to potentially prevent SUDEP.
Article
Clinical Neurology
Eugen Trinka, Taoufik Alsaadi, Hiroko Goji, Taketoshi Maehara, Satoru Takahashi, Julia Jacobs, Rosaria Renna, Francisco Jose Gil-Lopez, Rob McMurray, Ricardo Sainz-Fuertes, Vicente Villanueva
Summary: This study aimed to evaluate the effectiveness and tolerability of PER in the treatment of idiopathic generalized epilepsy under real-world conditions. The results showed that PER had good effectiveness and tolerability in people with idiopathic generalized epilepsy in clinical practice, consistent with clinical trial evidence.