Acta Epileptologica

Abstract Background The SLC2A1 gene plays a vital role in brain energy metabolism. SLC2A1 variants have been reported to be associated with early-onset refractory seizures. This study aims to explore the association between the SLC2A1 gene and late-onset epilepsy. Methods Trios-based whole-exome sequencing was performed on patients with epilepsy without acquired etiologies. The pathogenicity of the variants was assessed according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Results A total of 14 heterozygous SLC2A1 variants were identified in 16 unrelated families. The variants were evaluated as “pathogenic” or “likely pathogenic” according to the ACMG guidelines. Ten cases (62.5%) presented with infantile onset seizures and developmental delay/intellectual disability and were diagnosed with developmental and epileptic encephalopathy (DEE). The other six cases (37.5%) exhibited late-onset seizures and normal development. They were diagnosed with idiopathic partial epilepsy ( n = 2) or idiopathic generalized epilepsy ( n = 4). Further analysis showed that DEE-associated variants tended to cluster in the transmembrane region, whereas the mild epilepsy-associated variants tended to locate in regions outside the transmembrane region, suggesting a potential molecular sub-regional effect. A total of 15 cases had delayed diagnosis, with the longest delay being 22 years. The SLC2A1 expression stage, which is expressed at relatively high level throughout the whole life span, from the embryonic to adult stages with two peaks at approximately four and 14 years, is generally consistent with the seizure onset age. In addition, patients with early-onset age had variants that were potentially associated with severe damage, suggesting a potential correlation between the age of disease onset and the damaging effects of the variants. Conclusions SLC2A1 variants are associated with late-onset epilepsy, which is consistent with the genetic-dependent stage feature of SLC2A1 . Early genetic diagnosis is important for treatment of patients with SLC2A1 variants.

Dongming Zhang

Jing Guo

Zisheng Lin

Hongjun Yan

Kai Peng

Linxia Fei

Qiongxiang Zhai

Dongfang Zou

Jiayi Zhong

Yan Ding

Hong Ye

Pengyu Wang

Jie Wang

Sheng Luo

Bingmei Li

Bin Li

Weiping Liao

SLC2A1 variants cause late-onset epilepsy and the genetic-dependent stage feature

SLC2A1变异导致迟发性癫痫及遗传依赖性阶段特征

Abstract Background SCN1A is the most well-recognized and commonly mutated gene related to epilepsy. This study analyzed the characteristic spatial and frequency distributions of SCN1A mutations, aiming to provide important insight into the mutagenesis etiopathology of SCN1A -associated epilepsy. Methods Epilepsy-associated SCN1A variants were retrieved from the SCN1A mutation database, the HGMD database, and literature reviews. The base substitutions, mutation frequencies in CpG dinucleotides, and spatial distributions of mutations in terms of exons and structural domains were analyzed. Results A total of 2621 SCN1A variants were identified in 5106 unrelated cases. The most common type was missense mutation, followed by frameshift mutations and splice site mutations. Among the missense mutations, transitions within CpG dinucleotides were much more recurrently identified than transitions within non-CpG dinucleotides, and the most common type was the G &gt; A transition. Among the nonsense mutations, the most predominant type of single-base substitution was the C &gt; T transition, among which 75.3% (235/312) were within CpG sites. The most common “hotspot” codons for missense mutations were codons 101, 946, and 1783; while for nonsense mutations it was codon 712. One-base deletion or insertion was the most common type of frameshift mutation, causing protein truncation. The three most common frameshift mutations were c.5536_5539delAAAC, c.4554dupA, and c.5010_5013delGTTT. Splice mutations were the most frequently identified in exon 4 with a hotspot site c.602 + 1G &gt; A. The spatial distribution of missense mutations showed that exons 22 and 4 had the highest mutation density (111 and 84 mutations per 100 bp, respectively), and exon 12 had the lowest mutation density, with 4 mutations per 100 bp. Further distribution analysis of the protein domains revealed that missense mutations were more common in the pore region and voltage sensor (231 mutations per 100 amino acids, respectively), and the protein truncation mutations were distributed evenly among the domains. Conclusions SCN1A mutations tend to cluster at distinct sites, depending on the characteristic CpG dinucleotides, exons, and functional domains. Higher mutation density in particular regions, such as exon 22 and exon 4, offers promising targets for therapeutic genetic interventions.

Mengwen Zhang

Kang Liu

Jiayuan Zhao

Jiayuan Zhang

Xuqing Lin

Bin Tang

Na He

Characteristic spatial and frequency distribution of mutations in SCN1A

SCN1A突变的空间和频率分布特征

Abstract Background In this study, we aimed to assess the efficacy of surgical treatment in children with drug-refractory infantile epileptic spasms syndrome (IESS) and examine the factors influencing the post-surgical outcomes. Methods The clinical data of 30 children (18 males and 12 females) with epileptic spasms (ES) who underwent surgery at the Epilepsy Center of Shenzhen Children’s Hospital between June 2018 and June 2020 were retrospectively analyzed. Post-surgical outcomes were evaluated using the Engel Epilepsy Surgery Outcome Scale. Scalp electroencephalography and developmental quotient were assessed preoperatively and postoperatively. Univariate analysis and exact logistic regression analyses were used to identify the factors affecting the postoperative efficacy. Results Of the 30 patients who underwent surgical resection, 22 (73.3%) achieved Engel’s class I–II outcomes. Additionally, motor and cognitive functions improved in 14 patients (46.7%). The development of 12 (40%) patients remained at the preoperative development level. The median number of antiseizure medications taken preoperatively was 5.27 (range 2–10), which decreased to 1.90 (range 0–4) at the last follow-up. Seizure duration, etiology, positive positron emission tomography-magnetic resonance imaging (PET-MRI), surgery type, and lesion location were significantly correlated with the postoperative efficacy ( P &lt; 0.05). Positive PET/MRI findings and lesion location predicted independently the postoperative outcomes. Permanent impairments of motor or language function were rare, with only two cases reporting hydrocephalus and one reporting hemiplegia. Conclusions Surgery is an effective treatment option for children with IESS. Early referral and comprehensive preoperative evaluation are essential for identification of surgically treatable structural lesions. The primary surgically treatable cause is cortical malformation, followed by perinatal brain injury. Hemispheric disconnection is a preferred surgical approach. Positive PET/MRI findings and lesion location predicted the postoperative outcomes.

Xueyan Cao

Xin Ding

Fengjun Zhu

Li Chen

Yan Chen

Yang Sun

Lin Li

Zeshi Tan

Cong Li

Yi Yao

Qiru Su

Dezhi Cao

Surgical outcomes of drug-refractory infantile epileptic spasms syndrome and related prognostic factors: a retrospective study

药物难治性婴儿痉挛综合征的手术结果及相关预后因素：一项回顾性研究

Abstract Background Rauvolfia vomitoria ( R. vomitoria ) is a plant of economic importance due to its diverse ethnomedicinal properties, including the anticonvulsant effect. In this study, we studied the antiseizure and neuroprotective potentials of R. vomitoria extracts against pentylenetetrazol (PTZ)-induced kindling. Methods Twenty-five adult Swiss mice (25–30 g) were assigned to five groups ( n = 5): control group, PTZ treatment group, and PTZ treatment after receiving oral R. vomitoria crude extract (100 mg/kg), R. vomitoria phenol extract (50 mg/kg) or sodium valproate (15 mg/kg) every 48 h for 28 days. Seizure scores, cognitive behavioral tests including novel object test, Y-maze test, and the elevated plus maze test, as well as brain neurochemicals and histomorphology studies, were performed. Results Compared with the control group, the PTZ group showed comparable body weight and durations in closed and open arms ( P &gt; 0.05), but preference for familiar objects, significant ( P &lt; 0.05) spontaneous alternation, increased monoamine oxidase activity and nitric oxide level, and Nissl chromatolysis in the temporal lobe structures including the cortex, hippocampus, and amygdala. R. vomitoria phenol extract pretreatment significantly ( P &lt; 0.05) reduced seizures, prevented adverse cognitive behaviors, decreased the nitric oxide level, and reduced the temporal lobe Nissl chromatolysis compared with the R. vomitoria crude extract pretreatment group and the sodium valproate pretreatment groups. Conclusions Thus, R. vomitoria phenol extract showed promising results against seizures and potential for general brain protection, suggesting that the anticonvulsant property of R. vomitoria may be attributed to its phenol constituent. More studies are needed to delineate the mechanisms of its action.

Moses B. Ekong

Okokon O. Bassey

Deborah I. Ebeh

Godslove D. Usukuma

Darlington C. Samuel

Rosemary B. Bassey

Aniekan I. Peter

Christopher C. Mbadugha

Jude E. Okokon

Monday I. Akpanabiatu

Rauvolfia vomitoria phenol extract relieves pentylenetetrazol-induced seizures in Swiss mice and protects some temporal lobe structures

萝芙木酚提取物缓解戊四氮诱导的瑞士小鼠癫痫发作并保护部分颞叶结构

Abstract Unprovoked seizures in early life are one of the most severe conditions in pediatric neurology, and are often associated with long-lasting cognitive and behavioral deficits, as well as pharmacoresistant epilepsy in adulthood in some conditions. Unillustrated mechanisms greatly restrict the development of preventive strategies for early-life seizures (ELSs) related neuronal impairments. The recent groundbreaking study published in The Journal of Clinical Investigation represents a giant leap forward in understanding the complex pathogenesis mechanism and developing targeted therapies for ELS related neuronal impairments. The authors conducted elegant experiments to locate the activated pyramidal neuron subpopulation in the hippocampus and demonstrated the altered functions of (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)-type glutamate receptors (AMPARs). And we believe that the conclusions of this study may assist in further translational efforts to identify preventive targets for neurological disorders associated with early life seizures and propose new avenues for further exploration in this field.

Yingying Tang

Xiongfeng Guo

Mengqi Yan

Cenglin Xu

“Catch me if you can” - locating the “Black Sheep” neurons after early-life seizures

“抓住我，如果你能”——在早期生活癫痫后定位“害群之马”神经元

短名	Acta Epileptol.
Journal Impact	1.28
国际分区	CLINICAL NEUROLOGY(Q4)

出版信息	出版商: BioMed Central Ltd，出版周期: ，期刊类型: journal，开源期刊: 否
基本数据	创刊年份: 2019，原创研究文献占比: ，自引率:， Gold OA占比:

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SLC2A1 variants cause late-onset epilepsy and the genetic-dependent stage feature

Characteristic spatial and frequency distribution of mutations in SCN1A

Surgical outcomes of drug-refractory infantile epileptic spasms syndrome and related prognostic factors: a retrospective study

Rauvolfia vomitoria phenol extract relieves pentylenetetrazol-induced seizures in Swiss mice and protects some temporal lobe structures

“Catch me if you can” - locating the “Black Sheep” neurons after early-life seizures

Characteristic spatial and frequency distribution of mutations in SCN1A

SLC2A1 variants cause late-onset epilepsy and the genetic-dependent stage feature

Rauvolfia vomitoria phenol extract relieves pentylenetetrazol-induced seizures in Swiss mice and protects some temporal lobe structures

Surgical outcomes of drug-refractory infantile epileptic spasms syndrome and related prognostic factors: a retrospective study

“Catch me if you can” - locating the “Black Sheep” neurons after early-life seizures

ISSN	2096-9384, 2524-4434
h-index	7