Study of genetic variants and their clinical significance in Mexican pediatric patients with epilepsy.

BACKGROUND: The use of novel and accurate techniques to identify genetic variants (with or without a record in the National Center for Biotechnology Information (NCBI) database) improves diagnosis, prognosis, and therapeutics for patients with epilepsy, especially in populations for whom such techniques exist. The aim of this study was to find a genetic profile in Mexican pediatric epilepsy patients by focusing on ten genes associated with drug-resistant epilepsy (DRE). METHODS: This was a prospective, analytical, cross-sectional study of pediatric patients with epilepsy. Informed consent was granted by the patients' guardians or parents. Genomic DNA from the patients was sequenced using next-generation sequencing (NGS). For statistical analysis, Fisher's exact, Chi-square or Mann-Whitney U, and OR (95% CI) tests were performed, with significance values of p < 0.05. RESULTS: Fifty-five patients met the inclusion criteria (female 58.2%, ages 1-16 years); 32 patients had controlled epilepsy (CTR), and 23 had DRE. Four hundred twenty-two genetic variants were identified (71.3% with a known SNP registered in the NCBI database). A dominant genetic profile consisting of four haplotypes of the SCN1A, CYP2C9, and CYP2C19 genes was identified in most of the patients studied. When comparing the results between patients with DRE and CTR, the prevalence of polymorphisms in the SCN1A (rs10497275, rs10198801, and rs67636132), CYP2D6 (rs1065852), and CYP3A4 (rs2242480) genes showed statistical significance (p = 0.021). Finally, the number of missense genetic variants in patients in the nonstructural subgroup was significantly higher in DRE than in CTR (1 [0-2] vs. 3 [2-4]; p = 0.014). CONCLUSIONS: The Mexican pediatric epilepsy patients included in this cohort presented a characteristic genetic profile infrequent in the Mexican population. SNP rs1065852 (CYP2D6*10) is associated with DRE, especially with nonstructural damage. The presence of three genetic alterations affecting the CYP2B6, CYP2C9, and CYP2D6 cytochrome genes is associated with nonstructural DRE.

Boron-containing compounds on neurons: Actions and potential applications for treating neurodegenerative diseases.

Boron-containing compounds (BCC) exert effects on neurons. After the expanding of both the identification and synthesis of new BCC, novel effects in living systems have been reported, many of these involving neuronal action. In this review, the actions of BCC on neurons are described; the effects have been inferred by boron deprivation or addition. Also, the effects can be related to those mediated by interaction on ionic channels, G-protein coupled receptors, or other receptors exerting modification on neuronal behavior. Additionally, BCC have exhibited effects by the modulation of inflammation or oxidative processes. BCC are expanding as drugs. Deprivation of boron sources from the diet shows the role of some natural BCC. However, the observations of several new synthesized compounds suggest their ability to act with attractive potency, efficacy, and long-term action on neuronal receptors or processes related with the origin and evolution of neurodegenerative processes. The details of BCC-target interactions are currently being elucidated in progress, as those observed from BCC-protein crystal complexes. Taking all of the above into account, the expansion is presumably near to having studies on the application of BCC as drugs on specific targets for treating neurodegenerative diseases.

Cannabinoids: A New Perspective on Epileptogenesis and Seizure Treatment in Early Life in Basic and Clinical Studies.

Neural hyperexcitability in the event of damage during early life, such as hyperthermia, hypoxia, traumatic brain injury, status epilepticus, or a pre-existing neuroinflammatory condition, can promote the process of epileptogenesis, which is defined as the sequence of events that converts a normal circuit into a hyperexcitable circuit and represents the time that occurs between the damaging event and the development of spontaneous seizure activity or the establishment of epilepsy. Epilepsy is the most common neurological disease in the world, characterized by the presence of seizures recurring without apparent provocation. Cannabidiol (CBD), a phytocannabinoid derived from the subspecies Cannabis sativa (CS), is the most studied active ingredient and is currently studied as a therapeutic strategy: it is an anticonvulsant mainly used in children with catastrophic epileptic syndromes and has also been reported to have anti-inflammatory and antioxidant effects, supporting it as a therapeutic strategy with neuroprotective potential. However, the mechanisms by which CBD exerts these effects are not entirely known, and the few studies on acute and chronic models in immature animals have provided contradictory results. Thus, it is difficult to evaluate the therapeutic profile of CBD, as well as the involvement of the endocannabinoid system in epileptogenesis in the immature brain. Therefore, this review focuses on the collection of scientific data in animal models, as well as information from clinical studies on the effects of cannabinoids on epileptogenesis and their anticonvulsant and adverse effects in early life.