The Food and Drug Administration(FDA) has approved two mechanismbased treatments for tuberous sclero-sis complex(TSC)-everolimus and vigabatrin. However, these treatments have not been systematically studied in indivi...The Food and Drug Administration(FDA) has approved two mechanismbased treatments for tuberous sclero-sis complex(TSC)-everolimus and vigabatrin. However, these treatments have not been systematically studied in individuals with TSC and severe autism. The aim of this review is to identify the clinical features of severe autism in TSC, applicable preclinical models, and potential barriers that may warrant strategic planning in the design phase of clinical trial development. A comprehensive search strategy was formed and searched across Pub Med, Embase and SCOPUS from their inception to 2/21/12, 3/16/12, and 3/12/12 respectively. After the final search date, relevant, updated articles were selected from Pub Med abstracts generated electronically and emailed daily from Pub Med. The references of selected articles were searched, and relevant articles were selected. A search of clinicaltrials.gov was completed using the search term "TSC" and "tuberous sclerosis complex". Autism has been reported in as many as 60% of individuals with TSC; however, review of the literature revealed few data to support clear classification of the severity of autism in TSC. Variability was identified in the diagnostic approach, assessment of cognition, and functional outcome among the reviewed studies and case reports. Objective outcome measures were not used in many early studies; however, diffusion tensor imaging of white matter, neurophysiologic variability in infantile spasms, and cortical tuber subcategories were examined in recent studies and may be useful for objective classification of TSC in future studies. Mechanism-based treatments for TSC are currently available. However, this literature review revealed two potential barriers to successful design and implementation of clinical trials in individuals with severe autism-an unclear definition of the population and lack of validated outcome measures. Recent studies of objective outcome measures in TSC and further study of applicable preclinical models present an opportunity to overcome these barriers.展开更多
Importance:Perampanel(PER)is used less extensively in children than in adults.Currently,there is a lack of data from PER clinical studies with large sample sizes in Chinese children and adolescents with epilepsy,espec...Importance:Perampanel(PER)is used less extensively in children than in adults.Currently,there is a lack of data from PER clinical studies with large sample sizes in Chinese children and adolescents with epilepsy,especially those with refractory epilepsy.Objective:To evaluate the effectiveness,retention,and safety of PER in the treatment of children and adolescents with epilepsy in China.Methods:This was a multicenter,prospective,observational study.Children and adolescents with epilepsy who received PER as adjunctive therapy were included.The primary effectiveness endpoint was the proportion of patients achieving a≥50%reduction in seizure frequency after 6 months of treatment compared to baseline.The secondary effectiveness endpoints included retention and seizure-free rates.The safety outcome was the incidence of treatment-emergent adverse events(TEAEs).Results:A total of 240 patients with epilepsy were enrolled in the study.Prior to initiating PER treatment,approximately 87.9%of them took two or more antiseizure medications.After a 6-month treatment regimen with PER,70.4%of the patients experienced a reduced seizure frequency of at least 50%,and 22.1%achieved complete seizure freedom.The retention rate was 90.2%.TEAEs were reported by 89 patients,leading to the discontinuation of PER in seven cases.No severe TEAEs were observed in this study.Interpretation:Under routine clinical conditions,PER demonstrated good effectiveness and retention in Chinese children with epilepsy,particularly in those with refractory epilepsy.展开更多
基金Supported by Grant 2K12NS001696-11A1(to Gipson TT)from the National Institute of Neurological Disorders and StrokeGrant 5T32HD007414-18(to Gerner G)from the National Institute of Child Health and Human Development
文摘The Food and Drug Administration(FDA) has approved two mechanismbased treatments for tuberous sclero-sis complex(TSC)-everolimus and vigabatrin. However, these treatments have not been systematically studied in individuals with TSC and severe autism. The aim of this review is to identify the clinical features of severe autism in TSC, applicable preclinical models, and potential barriers that may warrant strategic planning in the design phase of clinical trial development. A comprehensive search strategy was formed and searched across Pub Med, Embase and SCOPUS from their inception to 2/21/12, 3/16/12, and 3/12/12 respectively. After the final search date, relevant, updated articles were selected from Pub Med abstracts generated electronically and emailed daily from Pub Med. The references of selected articles were searched, and relevant articles were selected. A search of clinicaltrials.gov was completed using the search term "TSC" and "tuberous sclerosis complex". Autism has been reported in as many as 60% of individuals with TSC; however, review of the literature revealed few data to support clear classification of the severity of autism in TSC. Variability was identified in the diagnostic approach, assessment of cognition, and functional outcome among the reviewed studies and case reports. Objective outcome measures were not used in many early studies; however, diffusion tensor imaging of white matter, neurophysiologic variability in infantile spasms, and cortical tuber subcategories were examined in recent studies and may be useful for objective classification of TSC in future studies. Mechanism-based treatments for TSC are currently available. However, this literature review revealed two potential barriers to successful design and implementation of clinical trials in individuals with severe autism-an unclear definition of the population and lack of validated outcome measures. Recent studies of objective outcome measures in TSC and further study of applicable preclinical models present an opportunity to overcome these barriers.
文摘Importance:Perampanel(PER)is used less extensively in children than in adults.Currently,there is a lack of data from PER clinical studies with large sample sizes in Chinese children and adolescents with epilepsy,especially those with refractory epilepsy.Objective:To evaluate the effectiveness,retention,and safety of PER in the treatment of children and adolescents with epilepsy in China.Methods:This was a multicenter,prospective,observational study.Children and adolescents with epilepsy who received PER as adjunctive therapy were included.The primary effectiveness endpoint was the proportion of patients achieving a≥50%reduction in seizure frequency after 6 months of treatment compared to baseline.The secondary effectiveness endpoints included retention and seizure-free rates.The safety outcome was the incidence of treatment-emergent adverse events(TEAEs).Results:A total of 240 patients with epilepsy were enrolled in the study.Prior to initiating PER treatment,approximately 87.9%of them took two or more antiseizure medications.After a 6-month treatment regimen with PER,70.4%of the patients experienced a reduced seizure frequency of at least 50%,and 22.1%achieved complete seizure freedom.The retention rate was 90.2%.TEAEs were reported by 89 patients,leading to the discontinuation of PER in seven cases.No severe TEAEs were observed in this study.Interpretation:Under routine clinical conditions,PER demonstrated good effectiveness and retention in Chinese children with epilepsy,particularly in those with refractory epilepsy.
