Epilepsy is a neurological disease characterized by excessive and abnormal hyper-synchrony of electrical discharges of the brain and a predisposition to generate epileptic seizures resulting in a broad spectrum of neu...Epilepsy is a neurological disease characterized by excessive and abnormal hyper-synchrony of electrical discharges of the brain and a predisposition to generate epileptic seizures resulting in a broad spectrum of neurobiological insults,imposing psychological,cognitive,social and also economic burdens to the sufferer.Voltage-gated sodium channels(VGSCs)are essential for the generation and propagation of action potentials throughout the central nervous system.Dysfunction of these channels has been implicated in the pathogenesis of epilepsy.VGSC inhibitors have been demonstrated to act as anticonvulsants to suppress the abnormal neuronal firing underlying epileptic seizures,and are used for the management and treatment of both genetic-idiopathic and acquired epilepsies.We discuss the forms of idiopathic and acquired epilepsies caused by VGSC mutations and the therapeutic efficacy of VGSC blockers in idiopathic,acquired and pharmacoresistant forms of epilepsy in this review.We conclude that there is a need for better alternative therapies that can be used alone or in combination with VGSC inhibitors in the management of epilepsies.The current anti-seizure medications(ASMs)especially for pharmacoresistant epilepsies and some other types of epilepsy have not yielded expected therapeutic efficacy partly because they do not show subtype-selectivity in blocking sodium channels while also bringing side effects.Therefore,there is a need to develop novel drug cocktails with enhanced selectivity for specific VGSC isoforms,to achieve better treatment of pharmacoresistant epilepsies and other types of epileptic seizures.展开更多
Epileptic seizures induce overexpression of P-glycoprotein in the blood-brain barrier. However, it is unclear whether hippocampal neurons also overexpress P-glycoprotein following seizure. This study confirmed that th...Epileptic seizures induce overexpression of P-glycoprotein in the blood-brain barrier. However, it is unclear whether hippocampal neurons also overexpress P-glycoprotein following seizure. This study confirmed that the clinical manifestation, pathological characteristics and electroencephalography in the rat model of lithium-pilocarpine-induced mesial temporal lobe epilepsy were consistent with clinical reports of mesial temporal lobe epilepsy in humans.Immunohistochemistry staining demonstrated that P-glycoprotein positive staining was found in neurons in the pyramidal layer of the hippocampus. Westem blot assay and real-time polymerase chain reaction revealed that P-glycoprotein overexpression was exhibited in the CA1, CA3, and dentate gyrus of the hippocampus at 24 and 60 days following model induction, but no significant dffierence was detected in the same region at various time points. These results indicate that seizures led to overexpression of P-glycoprotein in neurons of the hippocampus, but no evidence was found for a positive association between P-glycoprotein expression and seizure frequency.展开更多
Background:Due to the tradition of carbohydrate-rich diet,challenges exist for ketogenic diet(KD)implementation in Northwest China.This study was aimed to investigate the efficacy and tolerability of KD therapy admini...Background:Due to the tradition of carbohydrate-rich diet,challenges exist for ketogenic diet(KD)implementation in Northwest China.This study was aimed to investigate the efficacy and tolerability of KD therapy administered with gradual initiation protocols in Chinese children with pharmacoresistant epilepsy in Northwest China.Methods:In this single-center study,55 children with drug-resistant epilepsy were enrolled from June 2013 to June 2019.The efficacy of KD,reasons for discontinuation,duration of retention and rate of adverse events were evaluated.Results:Fifty-five children aged from 2.2 months to 169.7 months were included,with a median age at KD initiation of 14.1 months,and 32 cases(58.2%)responded to the diet therapy at the last contact.The responder rates were 16.4%(9/55);36.4%(20/55),30.9%(17/55),27.3%(15/55)at 1,3,6 and 12 months,respectively.Univariate analysis indicated that the duration of epilepsy and the duration of KD therapy were predictors for KD effectiveness.Poor compliance and lack of response were main reasons for discontinuation of KD.There are a few side effects of KD,most of which were minor.Conclusions:The KD therapy with a gradual-initiation protocol is effective and tolerable for children with drug-resist-ant epilepsy in Northwest China.Early start of KD and KD duration of more than 6 months may be predictive factors for KD efficacy.展开更多
文摘Epilepsy is a neurological disease characterized by excessive and abnormal hyper-synchrony of electrical discharges of the brain and a predisposition to generate epileptic seizures resulting in a broad spectrum of neurobiological insults,imposing psychological,cognitive,social and also economic burdens to the sufferer.Voltage-gated sodium channels(VGSCs)are essential for the generation and propagation of action potentials throughout the central nervous system.Dysfunction of these channels has been implicated in the pathogenesis of epilepsy.VGSC inhibitors have been demonstrated to act as anticonvulsants to suppress the abnormal neuronal firing underlying epileptic seizures,and are used for the management and treatment of both genetic-idiopathic and acquired epilepsies.We discuss the forms of idiopathic and acquired epilepsies caused by VGSC mutations and the therapeutic efficacy of VGSC blockers in idiopathic,acquired and pharmacoresistant forms of epilepsy in this review.We conclude that there is a need for better alternative therapies that can be used alone or in combination with VGSC inhibitors in the management of epilepsies.The current anti-seizure medications(ASMs)especially for pharmacoresistant epilepsies and some other types of epilepsy have not yielded expected therapeutic efficacy partly because they do not show subtype-selectivity in blocking sodium channels while also bringing side effects.Therefore,there is a need to develop novel drug cocktails with enhanced selectivity for specific VGSC isoforms,to achieve better treatment of pharmacoresistant epilepsies and other types of epileptic seizures.
基金the Science and Technology Foundation of Guangdong Province,No.2009B060700049,2008B060600063the National Natural Science Foundation of China,No.10671213
文摘Epileptic seizures induce overexpression of P-glycoprotein in the blood-brain barrier. However, it is unclear whether hippocampal neurons also overexpress P-glycoprotein following seizure. This study confirmed that the clinical manifestation, pathological characteristics and electroencephalography in the rat model of lithium-pilocarpine-induced mesial temporal lobe epilepsy were consistent with clinical reports of mesial temporal lobe epilepsy in humans.Immunohistochemistry staining demonstrated that P-glycoprotein positive staining was found in neurons in the pyramidal layer of the hippocampus. Westem blot assay and real-time polymerase chain reaction revealed that P-glycoprotein overexpression was exhibited in the CA1, CA3, and dentate gyrus of the hippocampus at 24 and 60 days following model induction, but no significant dffierence was detected in the same region at various time points. These results indicate that seizures led to overexpression of P-glycoprotein in neurons of the hippocampus, but no evidence was found for a positive association between P-glycoprotein expression and seizure frequency.
基金This work was supported by the Shanxi Science and Technology Support Program(Grant number 2017SF-292).
文摘Background:Due to the tradition of carbohydrate-rich diet,challenges exist for ketogenic diet(KD)implementation in Northwest China.This study was aimed to investigate the efficacy and tolerability of KD therapy administered with gradual initiation protocols in Chinese children with pharmacoresistant epilepsy in Northwest China.Methods:In this single-center study,55 children with drug-resistant epilepsy were enrolled from June 2013 to June 2019.The efficacy of KD,reasons for discontinuation,duration of retention and rate of adverse events were evaluated.Results:Fifty-five children aged from 2.2 months to 169.7 months were included,with a median age at KD initiation of 14.1 months,and 32 cases(58.2%)responded to the diet therapy at the last contact.The responder rates were 16.4%(9/55);36.4%(20/55),30.9%(17/55),27.3%(15/55)at 1,3,6 and 12 months,respectively.Univariate analysis indicated that the duration of epilepsy and the duration of KD therapy were predictors for KD effectiveness.Poor compliance and lack of response were main reasons for discontinuation of KD.There are a few side effects of KD,most of which were minor.Conclusions:The KD therapy with a gradual-initiation protocol is effective and tolerable for children with drug-resist-ant epilepsy in Northwest China.Early start of KD and KD duration of more than 6 months may be predictive factors for KD efficacy.
