The new antiepileptic drugs perampanel,retigabine,rufinamide and stiripentol have been recently approved for different epilepsy types.Being them an innovation in the antiepileptics armamentarium,a lot of investigation...The new antiepileptic drugs perampanel,retigabine,rufinamide and stiripentol have been recently approved for different epilepsy types.Being them an innovation in the antiepileptics armamentarium,a lot of investigations regarding their pharmacological properties are yet to be performed.Besides,considering their broad anticonvulsant activities,an extension of their therapeutic indications may be worthy of investigation,especially regarding other seizure types as well as other central nervous system disorders.Although different liquid chromatographic(LC)methods coupled with ultraviolet,fluorescence,mass or tandem-mass spectrometry detection have already been developed for the determination of perampanel,retigabine,rufinamide and stiripentol,new and more cost-effective methods are yet required.Therefore,this review summarizes the main analytical aspects regarding the liquid chromatographic methods developed for the analysis of perampanel,retigabine(and its main active metabolite),rufinamide and stiripentol in biological samples and pharmaceutical dosage forms.Furthermore,the physicochemical and stability properties of the target compounds will also be addressed.Thus,this review gathers,for the first time,important background information on LC methods that have been developed and applied for the determination of perampanel,retigabine,rufinamide and stiripentol,which should be considered as a starting point if new(bio)analytical techniques are aimed to be implemented for these drugs.展开更多
BACKGROUND Perampanel(PER),a third-generation antiepileptic drug,is a selective and noncompetitiveα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist,and has been approved for the treatment of ad...BACKGROUND Perampanel(PER),a third-generation antiepileptic drug,is a selective and noncompetitiveα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist,and has been approved for the treatment of adults and adolescents with focal epilepsy.However,there are only a few studies about the efficacy and tolerability of PER in young children with multidrug-resistant epilepsy.In this case,we aimed to share our clinical experience in this group.CASE SUMMARY A 4-year-old boy without perinatal asphyxia and familial history of epilepsy began to have ictal seizures from age 14 mo,with jerky movement of four limbs and head nodding.Abnormal multifocal discharge and background activity were recorded through electroencephalography,and no pathogenic mutation was found in the whole exome sequencing for the patient and his parents.He had received valproate,levetiracetam,topiramate,oxcarbazepine,clonazepam and lacosamide sequentially at different times,but he still had frequent seizures even after vagus nerve stimulation(VNS)implantation.He was diagnosed with idiopathic multidrug-resistant epilepsy.However,his seizure frequency was significantly reduced after PER administration in a dose-dependent manner,and better cognitive behavior was observed.In addition,the adverse reactions of anger and aggression also appeared.CONCLUSION PER is effective as add-on therapy for young children with multidrug-resistant epilepsy who have previously undergone VNS implantation.展开更多
Background NR2F1 mutations are associated with Bosch-Boonstra-Schaaf optic atrophy syndrome(BBSOAS).Although~46.7%of BBSOAS patients present with epilepsy,which is always drug-resistant and associated with higher rate...Background NR2F1 mutations are associated with Bosch-Boonstra-Schaaf optic atrophy syndrome(BBSOAS).Although~46.7%of BBSOAS patients present with epilepsy,which is always drug-resistant and associated with higher rates of behavioral and cognitive problems,the treatment and outcomes of NR2F1-related epilepsy have rarely been described.Here,we present new cases of BBSOAS-related epilepsy and summarize all previously reported cases to explore the effective treatment for this type of epilepsy.Methods We identified six new Chinese cases of BBSOAS with epilepsy.Five different de novo heterozygous NR2F1 mutations were identified in these cases,including two novel mutations c.365G>T,p.Cys122Phe and c.449G>T,p.Gly150Val.By combining the six cases and 14 previously reported cases,we analyzed the characteristics and treatment outcomes of NR2F1-related epilepsy.Results Twelve of the 20 patients(60%)had infantile epileptic spasms,while the other patients had generalized tonic/tonic-clonic,focal,myoclonic,absence,or unclassified seizures.Several anti-seizure medications,steroids,and a ketogenic diet were administered in these cases.However,seizures were controlled in only 50%of previously reported cases,while all of the six new cases became seizure-free after perampanel as an add-on treatment.The average time from the addition of perampanel to seizure control was 7.33±4.59 months(range,1–12 months).The median time to seizure freedom was 14 months(1–32 months,>19 months in 3 cases).The average dosage of perampanel needed for epilepsy control was 0.22±0.17 mg/kg per day.Conclusions In this paper,we comprehensively summarized the clinical characteristics,treatments and outcomes of NR2F1-related epilepsy for the first time.Perampanel exhibits dramatic efficacy for NR2F1-related epilepsy.This will help optimize the treatment of this type of epilepsy and provide clues for its pathogenic mechanisms.The two novel mutations expand the genotype spectrum of this disease.展开更多
基金supported by Banco Santander/Totta(Portugal)through the fellowship BID/ICI-FCS/CICS/Santander UniversidadesUBI/2017by Foundation for Science and Technology(FCT)through the fellowship SFRH/BD/136028/2018+3 种基金by FEDER funds through the POCI-COMPETE 2020-Operational Program Competitiveness and Internationalization in Axis I(Project No.POCI-01-0145FEDER-007491)National Funds by FCT(Project No.UIDB/00709/2020and Project No.UIDP/00709/2020)the support provided by FEDER funds through the“Programa Operacional do Centro”(Project No.CENTRO-010145-FEDER-000013)。
文摘The new antiepileptic drugs perampanel,retigabine,rufinamide and stiripentol have been recently approved for different epilepsy types.Being them an innovation in the antiepileptics armamentarium,a lot of investigations regarding their pharmacological properties are yet to be performed.Besides,considering their broad anticonvulsant activities,an extension of their therapeutic indications may be worthy of investigation,especially regarding other seizure types as well as other central nervous system disorders.Although different liquid chromatographic(LC)methods coupled with ultraviolet,fluorescence,mass or tandem-mass spectrometry detection have already been developed for the determination of perampanel,retigabine,rufinamide and stiripentol,new and more cost-effective methods are yet required.Therefore,this review summarizes the main analytical aspects regarding the liquid chromatographic methods developed for the analysis of perampanel,retigabine(and its main active metabolite),rufinamide and stiripentol in biological samples and pharmaceutical dosage forms.Furthermore,the physicochemical and stability properties of the target compounds will also be addressed.Thus,this review gathers,for the first time,important background information on LC methods that have been developed and applied for the determination of perampanel,retigabine,rufinamide and stiripentol,which should be considered as a starting point if new(bio)analytical techniques are aimed to be implemented for these drugs.
文摘BACKGROUND Perampanel(PER),a third-generation antiepileptic drug,is a selective and noncompetitiveα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist,and has been approved for the treatment of adults and adolescents with focal epilepsy.However,there are only a few studies about the efficacy and tolerability of PER in young children with multidrug-resistant epilepsy.In this case,we aimed to share our clinical experience in this group.CASE SUMMARY A 4-year-old boy without perinatal asphyxia and familial history of epilepsy began to have ictal seizures from age 14 mo,with jerky movement of four limbs and head nodding.Abnormal multifocal discharge and background activity were recorded through electroencephalography,and no pathogenic mutation was found in the whole exome sequencing for the patient and his parents.He had received valproate,levetiracetam,topiramate,oxcarbazepine,clonazepam and lacosamide sequentially at different times,but he still had frequent seizures even after vagus nerve stimulation(VNS)implantation.He was diagnosed with idiopathic multidrug-resistant epilepsy.However,his seizure frequency was significantly reduced after PER administration in a dose-dependent manner,and better cognitive behavior was observed.In addition,the adverse reactions of anger and aggression also appeared.CONCLUSION PER is effective as add-on therapy for young children with multidrug-resistant epilepsy who have previously undergone VNS implantation.
文摘Background NR2F1 mutations are associated with Bosch-Boonstra-Schaaf optic atrophy syndrome(BBSOAS).Although~46.7%of BBSOAS patients present with epilepsy,which is always drug-resistant and associated with higher rates of behavioral and cognitive problems,the treatment and outcomes of NR2F1-related epilepsy have rarely been described.Here,we present new cases of BBSOAS-related epilepsy and summarize all previously reported cases to explore the effective treatment for this type of epilepsy.Methods We identified six new Chinese cases of BBSOAS with epilepsy.Five different de novo heterozygous NR2F1 mutations were identified in these cases,including two novel mutations c.365G>T,p.Cys122Phe and c.449G>T,p.Gly150Val.By combining the six cases and 14 previously reported cases,we analyzed the characteristics and treatment outcomes of NR2F1-related epilepsy.Results Twelve of the 20 patients(60%)had infantile epileptic spasms,while the other patients had generalized tonic/tonic-clonic,focal,myoclonic,absence,or unclassified seizures.Several anti-seizure medications,steroids,and a ketogenic diet were administered in these cases.However,seizures were controlled in only 50%of previously reported cases,while all of the six new cases became seizure-free after perampanel as an add-on treatment.The average time from the addition of perampanel to seizure control was 7.33±4.59 months(range,1–12 months).The median time to seizure freedom was 14 months(1–32 months,>19 months in 3 cases).The average dosage of perampanel needed for epilepsy control was 0.22±0.17 mg/kg per day.Conclusions In this paper,we comprehensively summarized the clinical characteristics,treatments and outcomes of NR2F1-related epilepsy for the first time.Perampanel exhibits dramatic efficacy for NR2F1-related epilepsy.This will help optimize the treatment of this type of epilepsy and provide clues for its pathogenic mechanisms.The two novel mutations expand the genotype spectrum of this disease.
