10 research outputs found
Vagus nerve stimulation (VNS) therapy update.
Epilepsy affects millions of people worldwide. Approximately one-third have pharmacoresistant epilepsy, and of these, the majority are not candidates for epilepsy surgery. Vagus nerve stimulation (VNS) therapy has been an option to treat pharmacoresistant seizures for 30 years. In this update, we will review the clinical data that support the device's efficacy in children, adolescents, and adults. We will also review its side-effect profile, quality of life and cost benefits, and the impact the device has on sudden unexpected death in epilepsy (SUDEP). We will then discuss candidate selection and provide guidance on dosing and future models. Vagus nerve stimulation therapy is an effective treatment for many seizure types and epilepsy syndromes with a predictable and benign side-effect profile that supports its role as the most commonly prescribed device to treat pharmacoresistant epilepsy. "This article is part of the Supplement issue Neurostimulation for Epilepsy.
HLA-A*31:01 and HLA-B*15:02 as Genetic Markers for Carbamazepine Hypersensitivity in Children
PSU33 Characteristics and Burden of Tuberous Sclerosis Complex: Results of a Patient and Caregiver Survey in the United States
Characterization of SETD1A haploinsufficiency in humans and Drosophila defines a novel neurodevelopmental syndrome
Defects in histone methyltransferases (HMTs) are major contributing factors in neurodevelopmental disorders (NDDs). Heterozygous variants of SETD1A involved in histone H3 lysine 4 (H3K4) methylation were previously identified in individuals with schizophrenia. Here, we define the clinical features of the Mendelian syndrome associated with haploinsufficiency of SETD1A by investigating 15 predominantly pediatric individuals who all have de novo SETD1A variants. These individuals present with a core set of symptoms comprising global developmental delay and/or intellectual disability, subtle facial dysmorphisms, behavioral and psychiatric problems. We examined cellular phenotypes in three patient-derived lymphoblastoid cell lines with three variants: p.Gly535Alafs*12, c.4582-2_4582delAG, and p.Tyr1499Asp. These patient cell lines displayed DNA damage repair defects that were comparable to previously observed RNAi-mediated depletion of SETD1A. This suggested that these variants, including the p.Tyr1499Asp in the catalytic SET domain, behave as loss-of-function (LoF) alleles. Previous studies demonstrated a role for SETD1A in cell cycle control and differentiation. However, individuals with SETD1A variants do not show major structural brain defects or severe microcephaly, suggesting that defective proliferation and differentiation of neural progenitors is unlikely the single underlying cause of the disorder. We show here that the Drosophila melanogaster SETD1A orthologue is required in postmitotic neurons of the fly brain for normal memory, suggesting a role in post development neuronal function. Together, this study defines a neurodevelopmental disorder caused by dominant de novo LoF variants in SETD1A and further supports a role for H3K4 methyltransferases in the regulation of neuronal processes underlying normal cognitive functioning