更新于：2024-11-01

Febrile Seizures Associated With Afebrile Seizures

与非热性惊厥相关的热性惊厥

更新于：2024-11-01

基本信息

别名

Febrile Seizures Associated with Afebrile Seizures、高热惊厥与高热惊厥相关

简介-

关联

项与与非热性惊厥相关的热性惊厥相关的药物

Diazepam

地西泮

靶点

GABAA receptor

作用机制

GABAA receptor激动剂

在研机构

Maruishi Pharmaceutical Co., Ltd. [+9]

原研机构

Waylis Therapeutics LLC

在研适应症

癫痫发作 [+11]

非在研适应症

急性反复发作

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期1963-11-15

100 项与与非热性惊厥相关的热性惊厥相关的临床结果

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100 项与与非热性惊厥相关的热性惊厥相关的转化医学

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0 项与与非热性惊厥相关的热性惊厥相关的专利（医药）

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项与与非热性惊厥相关的热性惊厥相关的文献（医药）

2024-10-03·Brain

Heterozygous variants in USP25 cause genetic generalized epilepsy

Article

作者: Deng, Wei-Yi ; Qu, Xiao-Chong ; Chen, Qian ; Shi, Yi-Wu ; Li, Wen-Bin ; Fan, Cui-Xia ; Liu, Xiao-Rong ; Liao, Wei-Ping ; He, Na ; Xie, Huan-Cheng ; Mei, Dao-Qi ; Wang, Jie ; You, Qiang-Long ; Shen, Nan-Xiang ; Gao, Jun-Ying ; Li, Jia ; Zhang, Ming-Rui ; Liang, Jin-Jie ; Chen, Li-Zhi ; Wang, Wen-Ting ; Li, Bing-Mei ; Ye, Zi-Long ; Liu, Wen-Zhe ; Li, Ling-Ying

AbstractUSP25 encodes ubiquitin-specific protease 25, a key member of the deubiquitinating enzyme family that is involved in neural fate determination. Although abnormal expression in Down's syndrome was reported previously, the specific role of USP25 in human diseases has not been defined.In this study, we performed trio-based whole exome sequencing in a cohort of 319 cases (families) with generalized epilepsy of unknown aetiology. Five heterozygous USP25 variants, including two de novo and three co-segregated variants, were determined in eight individuals affected by generalized seizures and/or febrile seizures from five unrelated families. The frequency of USP25 variants showed a significantly high aggregation in this cohort compared with the East Asian population and all populations in the gnomAD database. The mean age at onset of febrile and afebrile seizures were 10 months (infancy) and 11.8 years (juvenile), respectively. The patients achieved seizure freedom, except that one had occasional nocturnal seizures at the last follow-up. Two patients exhibited intellectual disability.Usp25 was expressed ubiquitously in mouse brain with two peaks, on embryonic Days 14–16 and postnatal Day 21, respectively. In human brain, likewise, USP25 is expressed in the fetus/early childhood stage and with a second peak at ∼12–20 years old, consistent with the seizure onset age in patients during infancy and in juveniles.To investigate the functional impact of USP25 deficiency in vivo, we established Usp25 knockout mice, which showed increased seizure susceptibility compared with wild-type mice in a pentylenetetrazol-induced seizure test.To explore the impact of USP25 variants, we used multiple functional detections. In HEK293 T cells, the variant associated with a severe phenotype (p.Gln889Ter) led to a significant reduction of mRNA and protein expressions but formed stable truncated dimers with an increment of deubiquitinating enzyme activities and abnormal cellular aggregations, indicating a gain-of-function effect. The p.Gln889Ter and p.Leu1045del variants increased neuronal excitability in mouse brain, with a higher firing ability in p.Gln889Ter. These functional impairments align with the severity of the observed phenotypes, suggesting a genotype–phenotype correlation. Hence, a moderate association between USP25 and epilepsy was noted, indicating that USP25 is potentially a predisposing gene for epilepsy.Our results from Usp25 null mice and the patient-derived variants indicated that USP25 would play an epileptogenic role via loss-of-function or gain-of-function effects. The truncated variant p.Gln889Ter would have a profoundly different effect on epilepsy. Together, our results underscore the significance of USP25 heterozygous variants in epilepsy, thereby highlighting the critical role of USP25 in the brain.

2024-08-01·Pediatric Neurology

Seizures in Children With Severe Acute Respiratory Syndrome Coronavirus 2 Infection

Article

作者: de Ceano-Vivas Lacalle, María ; Furones García, Marta ; de Miguel Lavisier, Begoña ; Bueno Barriocanal, Marta ; Molina Gutiérrez, Miguel Ángel ; García Sánchez, Paula ; Púa Torrejón, Ruth Camila ; Ruíz Domínguez, Jose Antonio ; López López, Rosario ; Rodríguez Mesa, María Dolores ; García Herrero, María Ángeles

BACKGROUNDAlthough respiratory symptoms are the most prominent manifestations of coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and especially the omicron variant, may cause neurological manifestations such as seizures. It remains unclear if specific variants of the virus increase the risk of seizures more than others.MATERIAL AND METHODSThis was a retrospective multicenter study of pediatric (zero to 16 years) patients with COVID-19 who attended five pediatric emergency departments in Madrid, Spain, between March 2020 and July 2022. An analysis of demographics, medical history, and seizure characteristics was conducted. The data obtained were correlated with the incidence of the different strains of SARS-CoV-2 in the Community of Madrid.RESULTSA total of 2411 seizures (infectious and noninfectious) were recorded, and 35 of them (1.4%) were positive for SARS-CoV-2. Of those 35 patients, 18 (51.4%) reported a history of previous seizures. The highest percentage of cases occurred when the omicron variant was the most prevalent (28 [80%] vs 7 [20%] before omicron variant). Typical febrile seizures accounted for 52.9% of the cases. No treatment was required in more than half (57.1%) of the cases.CONCLUSIONduring the emergence of the omicron variant, there has been an increase in the number of COVID-19-associated seizures. These findings highlight the need for SARS-CoV-2 screening in patients with febrile and afebrile seizures, in addition to other microbiological, biochemical, or neuroimaging tests, depending on the patient's age and clinical presentation.

2024-02-01·Epileptic Disorders

Cerebral hemiatrophy and hemiparesis following hemiclonic status epilepticus in Dravet syndrome

Article

作者: Espeche, Alberto ; Caraballo, Roberto ; Beltrán, Lucas ; Guzman, Ariel

AbstractDravet syndrome is currently considered as an developmental and epileptic encephalopathy and, recently, mandatory, alert, and exclusionary criteria have been proposed. Here, we describe three patients with Dravet syndrome with the typical early presentation including febrile and afebrile alternating hemiclonic seizures due to loss‐of‐function SCN1A variants. Subsequently, they developed episodes of febrile focal status epilepticus (SE) associated with hemiparesis and cerebral hemiatrophy with posterior focal seizures, as a consequence of Dravet syndrome. This sequence of events has been previously published in patients with Dravet syndrome and does not contradict the recent classification by the International League Against Epilepsy (ILAE). The ILAE guidance identifies “Focal neurological findings” as alert criteria and “MRI showing a causal focal lesion” as exclusionary criteria for making an initial diagnosis of Dravet syndrome at presentation. Our three patients would correspond to a severe phenotype, similar to the well‐known presentation of generalized atrophy following prolonged status epilepticus. Common genetic findings in cases of diffuse and unilateral brain involvement may help explain these clinical presentations. Further genotype–phenotype studies may provide additional insights into this electroclinical behavior.