Browsing by Subject "Epilepsies, Partial"
Now showing 1 - 2 of 2
- Results Per Page
- Sort Options
Item Discrimination Between Frontal and Temporal Lobe Epilepsy in Children(2006-05-15) Clark, Jennifer Paulette Holinbaugh; Silver, Cheryl H.Distinguishing between children with frontal lobe epilepsy (FLE) and children with temporal lobe epilepsy (TLE) can be difficult; however, in order to assure proper treatment and intervention it is important to accurately differentiate between these two groups. One of the intended goals of this study is to identify tabletop and behavioral rating measures that will assist in differentiating children with FLE from children with TLE. Another purpose of this study is to examine the utility of the Children's Executive Functions Scale (CEFS), a parent-report measure of executive functioning, in differentiating between children with FLE and TLE. Sixty children, ranging in age from 6 to 17, will be divided into two groups (a) children with frontal lobe epilepsy and (b) children with temporal lobe epilepsy. The participants will be evaluated using the Tower of London (TOL), The Wide Range Assessment of Memory and Learning - 2 (WRAML-2), the CEFS, and the Child Behavior Checklist (CBCL). It is hypothesized that children with FLE will display more impairment than children with TLE on both measures of executive functioning (the CEFS and the TOL). It is further hypothesized that children with RTLE will perform significantly worse visual memory components of the WRAML-2 than individuals with FLE or LTLE . It is expected that children with LTLE will perform worse than children with RTLE or FLE on verbal memory components of the WRAML-2. Finally, it is hypothesized that scores on the CBCL will reflect that children with TLE display a greater number of internalizing symptoms than children with FLE. The findings of this study could also have important implications in the understanding of deficits associated with FLE and TLE. Furthermore, the findings could suggest direction for future research and for treatment and interventions.Item Neural Mechanisms and Behaviors in Models of Conditional Nprl2 Loss(2020-08-01T05:00:00.000Z) Dentel, Brianne Marie; Johnson, Jane E.; Tu, Benjamin; Pascual, Juan M.; Tsai, PeterThe amino acid sensitive arm of mTORC1 regulation signals through the GATOR1 complex. Loss of function of GATOR1 contributes to several neurodevelopmental disorders and medically refractive epilepsy. Mutations to one of the essential subunits of GATOR1, NPRL2, are sufficient to cause focal epilepsy and schizophrenia; yet, little is known about its role in the nervous system. Here we demonstrate the loss of Nprl2 in excitatory cells in the neocortex and hippocampus is sufficient to cause mTOR-related pathology, decreased survival and spontaneous seizures. By inhibiting mTOR activity with rapamycin we were able to rescue brain size, seizures and survival. We also show that loss of Nprl2 results in a down-regulation of synaptic proteins, and several metabolic disruptions. Furthermore, we demonstrated that the significantly increased glycine was a primary mechanism which increased synaptic excitability. This suggests that targeting the glycine binding site on the NMDA receptor may be a targeted therapy for future study. We also demonstrated, in three different cell-specific conditional knockout models, distinct behavioral profiles which points to the importance of Nprl2 in various neurodevelopmental disorders. These findings demonstrate the multifaceted effects of Nprl2 loss in excitatory cells- which demonstrate seizures and early mortality; excitatory and inhibitory neurons- which had seizures, hyperactivity, social and learning deficits; inhibitory cells- which demonstrated severe hyperactivity, social and learning deficits; and Purkinje cell-specific loss- which had seizure susceptibility, reversal learning deficits and delayed-onset social deficits and altered PPI. These findings highlight the significant role NPRL2 has in the nervous system and future studies in these models will aid in understanding and potentially developing targeted therapies to address the molecular and cellular mechanisms underlying NDDs and seizures in NPRL2 loss.