Dravet Syndrome (DS) is a developmental epileptic encephalopathy characterized by drug-resistant seizures and other clinical features, including intellectual disability and behavioral, sleep, and gait problems. The pathogenesis is strongly connected to voltage-gated sodium channel dysfunction. The current consensus of seizure management in DS consists of a combination of conventional and recently approved drugs such as stiripentol, cannabidiol, and fenfluramine. Despite promising results in randomized clinical trials and extension studies, the prognosis of the developmental outcomes of patients with DS remains unfavorable. The article summarizes recent changes in the therapeutic approach to DS and discusses ongoing clinical research directions. Serotonergic agents under investigation show promising results and may replace less DS-specific medicines. The use of antisense nucleotides and gene therapy is focused not only on symptom relief but primarily addresses the underlying cause of the syndrome. Novel compounds, after expected safe and successful implementation in clinical practice, will open a new era for patients with DS. The main goal of causative treatment is to modify the natural course of the disease and provide the best neurodevelopmental outcome with minimum neurological deficit.

Introduction, Tuberous sclerosis complex (TSC) is an autosomal-dominant disorder caused by mutations inactivating TSC1 or TSC2 genes and characterized by the presence of tumors involving many organs, including the brain, heart, kidneys, and skin. Subependymal giant cell astrocytoma (SEGA) is a slow-growing brain tumor almost exclusively associated with TSC. State of the Art: Despite the fact that SEGAs are benign, they require well-considered decisions regarding the timing and modality of pharmacological or surgical treatment. In TSC children and adolescents, SEGA is the major cause of mortality and morbidity. Clinical Implications: Until recently, surgical resection has been the standard therapy for SEGAs but the discovery of the role of the mTOR pathway and the introduction of mTOR inhibitors to clinical practice changed the therapeutic landscape of these tumors. In the current paper, we discuss the pros and cons of mTOR inhibitors and surgical approaches in SEGA treatment. Future Directions: In 2021, the International Tuberous Sclerosis Complex Consensus Group proposed a new integrative strategy for SEGA management. In the following review, we discuss the proposed recommendations and report the results of the literature search for the latest treatment directions.

The basolateral amygdala (BLA) controls socio-emotional behaviors and is involved in the etiology of autism. We have recently shown that virtually every neuronal nitric oxide synthase (nNOS) positive cell is a GABAergic inhibitory interneuron in the mouse BLA. Here, stereology was used to quantify the number of nNOS-expressing interneurons in valproic acid (VPA)-exposed C57BL/6J (B6) and BTBR T⁺Itpr3^tf/J (BTBR) mice models of autism. Additionally, the protein and mRNA levels of nNOS in the BLA were quantitatively assessed by western blot and qRT-PCR analysis, respectively. Our results showed the decreased number of nNOS interneurons in the BLA of animal models relative to autism. Consistently, nNOS was significantly reduced in the VPA-exposed and BTBR mice at both protein and mRNA levels. Together, these preliminary findings suggest that down-regulation of nNOS may be an attractive target for the pharmacological intervention in autism.

Epilepsy, a neurological condition, is widely prevalent among individuals with intellectual disability (ID). It is well established that N-methyl-D-aspartate (NMDA) receptors play an important role in both epilepsy and ID. Autosomal dominant mutations in the GRIN2B gene, which encodes the GluN2B subunit of the NMDA receptor, have been reported to be associated with epilepsy and ID. However, the underlying mechanism of this association is not well-understood. In this study, we identified a novel GRIN2B mutation (c.3272A > C, p.K1091T) in a patient with epilepsy and ID. The proband was a one year and ten months old girl. GRIN2B variant was inherited from her mother. We further investigated the functional consequences of this mutation. Our findings revealed that the p.K1091T mutation created a Casein kinase 2 phosphorylation site. Using recombinant NMDA receptors containing the GluN2B-K1091T along with GluN1 in HEK 293T cells, we observed significant defects in its interactions with postsynaptic density 95. It is accompanied by reduced delivery of the receptors to the cell membrane and a decrease in glutamate affinity. Moreover, primary neurons expressing GluN2B-K1091T also exhibited impaired surface expression of NMDA receptors, a reduction in dendritic spine number and excitatory synaptic transmission. In summary, our study reports a novel GRIN2B mutation and provides functional characteristics of this mutation in vitro, thereby contributing to the understanding of GRIN2B variants in epilepsy and ID.