Different Forms Of Epilepsy Research Articles

Efficacy and tolerability of sulthiame in the treatment of epilepsy: a literature review

This review aims to summarize the available evidence on the efficacy and tolerability of sulthiame for different forms of epilepsy. The analysis of international publications suggests that sulthiame is considered as a first-line drug for the treatment of age-dependent epilepsy with central temporal spikes (rolandic epilepsy). Sulthiame is highly effective in children with epileptic encephalopathies manifesting with spike-and-wave activity during sleep, including Landau-Kleffner syndrome, as well as in patients with myoclonic seizures. The drug might be also effective in patients with other forms of focal epilepsy, including those resistant to therapy. The tolerability of sulthiame is higher that that of old antiepileptic drugs and even levetiracetam; thus, it is associated with a lower risk of treatment interruptions due to adverse events. Moreover, sulthiame can be used for behavioral disorders (such as hyperkinetic behavior, aggressiveness) and cognitive impairments. Sulthiame can be effective in patients with epilepsy and sleep apnea.

Presurgical evaluation algorithm of epilepsy and its practical significance

Objective: Evaluation of the efficacy of surgical treatment for different forms of epilepsy using individualized complex presurgical diagnostic algorithms.Materials and Methods: The study included 104 patients with localized unifocal forms of epilepsy and 48 patients with multifocal epilepsy. Among them, 68 (44.7%) were children and 84 (55.3%) were adults. Patients' age ranged from 2 to 63 years. All patients had frequent epileptic seizures and unsatisfactory results of medical treatment. Recurrent status epilepticus or serial seizures in the anamnesis were presented in 74 cases (48.7%). Medication for all patients before surgery treatment included from 1 to 8 antiepileptic drugs. Postsurgical follow-up lasted from 4 months to 16 years. Main examinations included: complete medical history, types of epileptic seizures, EEG or video-EEG, brain MRI. Additional examinations included: MRI - tractography and functional MRI, single-photon emission computed tomography (SPECT), positron emission tomography, subtraction ictal SPECT co-registered to MRI, and intraoperative corticography.Results: The use of presurgical evaluation algorithm made it possible to localize epileptogenic foci (EF) in all patients. The method of surgical intervention was chosen only of the received preoperative data. Seizures free (Engel Ia) was achieved in 67 (44.1%) patients. Single focal or nocturnal seizures (Engel Ib-c) were reported in 37 (24.3%) patients. Significant regression of the number of epileptic seizures (Engel II) was achieved in 28 (18.4%) cases, and moderate regression (Engel III) - in 12 (23.1%) patients. Absence of positive dynamics after surgery (Engel IV) occurred in 7 (4.6%) patients. Surgical complications occurred in 13 (8.6%) patients.Conclusions: Presurgical evaluation algorithm helped localize unifocal and multifocal EF, which allows choosing a surgical technique, accurately planning the stategy of intervention and carrying it out safely. In cases of surgical impact on EF, it is possible to achieve complete seizure control.

A Comprehensive Review on Anti-Inflammatory Response of Flavonoids in Experimentally-Induced Epileptic Seizures.

Flavonoids, a group of natural compounds with phenolic structure, are becoming popular as alternative medicines obtained from plants. These compounds are reported to have various pharmacological properties, including attenuation of inflammatory responses in multiple health issues. Epilepsy is a disorder of the central nervous system implicated with the activation of the inflammatory cascade in the brain. The aim of the present study was to summarize the role of various neuroinflammatory mediators in the onset and progression of epilepsy, and, thereafter, to discuss the flavonoids and their classes, including their biological properties. Further, we highlighted the modulation of anti-inflammatory responses achieved by these substances in different forms of epilepsy, as evident from preclinical studies executed on multiple epilepsy models. Overall, the review summarizes the available evidence of the anti-inflammatory potential of various flavonoids in epilepsy.

Lamotrigine (Sazar) in the treatment of epilepsy: four years of experience in Svt. Luka's Association of Medical institutions for the Diagnosis, Treatment, and Rehabilitation of Nervous System Diseases and Epilepsy

Aim. To assess the efficacy and tolerability of lamotrigine (Sazar) for various forms of epilepsy, based on long-term experience of Svt. Luka's Association of Medical Institutions for the Diagnosis, Treatment, and Rehabilitation of Nervous System Diseases and Epilepsy. We analyzed the data obtained during 4 years (from June 2018 to August 2022).Materials and methods. We evaluated the efficacy and tolerability of Sazar in 104 patients aged 3 to 37 years (87 children and 17 adults (12 women and 5 men)); their mean age was 9.7 years. The sample included 42 males and 62 females. All of them were treated at Svt. Luka's Association of Medical Institutions for the Diagnosis, Treatment, and Rehabilitation of Nervous System Diseases and Epilepsy.The sample included patients with structural and presumably structural focal epilepsy (n = 44), focal epilepsy of unknown etiology (n = 6), genetic and presumably genetic epilepsy and epileptic encephalopathies (n = 43), idiopathic epilepsy (n = 11).Sazar was used as a monotherapy in 38 patients, whereas 66 patients received it in combination with other antiepileptic drugs (AED) (Sazar + 1 AED in 48 patients; Sazar + 2 AED in 18 patients). Two patients initially receiving polytherapy were successfully transferred to Sazar monotherapy.The dose of Sazar varied between 75 and 400 mg/day. In the majority of patients, including all children, Sazar daily dose was split into 2 portions. Three adult patients received Cazar once a day either in the evening (n = 2) or in the morning (n = 1) at a dose of 200 mg/day. The follow-up time was between 6 months and over 4 years.Results and conclusion. Therapeutic remission was achieved in 47 out of 104 patients (45.2 %) receiving Sazar. As many as 35 patients (33.6 %) demonstrated an at least 50 % reduction in seizure frequency; 22 patients had no effect (21.2 %). None of the participants developed significant aggravation.Only 9 patients (8.6 %) discontinued Caser due to its initial low efficacy, while another 8 patients (7.6 %) stopped to receive Casar because it became ineffective after 6–12 months of treatment. In general, good therapeutic effect (remission or at least 50 % reduction in seizure frequency) was achieved in 82 out of 104 patients (78.8 %). Given the fact that this study included patients with severe epilepsy, we can conclude that treatment was very effective.Casar was most effective in patients with focal epilepsy (including structural, presumably structural, structural-genetic, and that of unidentified etiology) and idiopathic generalized epilepsy.The majority of the patients (n = 94; 90.4 %) demonstrated good tolerability of Casar. Casar-associated side effects were registered in 10 patients (9.6 %). Allergic skin rash was observed in 5 cases (4.8 %) and developed during the first 2 months of therapy. Allergic reactions accounted for 50 % of all side effects and were the only reason for Casar discontinuation due to poor tolerability.Two female patients of reproductive age started Sazar to reduce the valproate dose that caused severe menstrual disorders, weight gain, alopecia, and edema. Halving the dose of valproate (up to 750 mg/day) in combination with Casar significantly improved treatment tolerance. One patient gave birth to a healthy baby when she was receiving monotherapy with Sazar at a dose of 350 mg/day.Eight patients receiving Sazar reported a significant improvement in their mood and behavior (one patient that had earlier been diagnosed with depression discontinued antidepressants after Sazar initiation since she did not need them any longer). None of the patients reported any negative effects of Sazar on their memory, attention, mood, and behavior (as evaluated by patients and parents; in some cases, by a neuropsychologist).Patients’ adherence to treatment confirmed high Sazar efficacy and tolerability: 82 out of 104 patients (78.8 %) continued to receive the drug after 6 months of treatment and 69 patients (66.3 %) still continued it after 12 months of treatment. The follow-up period varied between 6 months and 4 years.Thus, our findings suggest high efficacy and good tolerability of long-term therapy with Sazar in patients with different forms of epilepsy.

Functional Effects of Epilepsy Associated KCNT1 Mutations Suggest Pathogenesis via Aberrant Inhibitory Neuronal Activity

KCNT1 (K+ channel subfamily T member 1) is a sodium-activated potassium channel highly expressed in the nervous system which regulates neuronal excitability by contributing to the resting membrane potential and hyperpolarisation following a train of action potentials. Gain of function mutations in the KCNT1 gene are the cause of neurological disorders associated with different forms of epilepsy. To gain insights into the underlying pathobiology we investigated the functional effects of 9 recently published KCNT1 mutations, 4 previously studied KCNT1 mutations, and one previously unpublished KCNT1 variant of unknown significance. We analysed the properties of KCNT1 potassium currents and attempted to find a correlation between the changes in KCNT1 characteristics due to the mutations and severity of the neurological disorder they cause. KCNT1 mutations identified in patients with epilepsy were introduced into the full length human KCNT1 cDNA using quick-change site-directed mutagenesis protocol. Electrophysiological properties of different KCNT1 constructs were investigated using a heterologous expression system (HEK293T cells) and patch clamping. All mutations studied, except T314A, increased the amplitude of KCNT1 currents, and some mutations shifted the voltage dependence of KCNT1 open probability, increasing the proportion of channels open at the resting membrane potential. The T314A mutation did not affect KCNT1 current amplitude but abolished its voltage dependence. We observed a positive correlation between the severity of the neurological disorder and the KCNT1 channel open probability at resting membrane potential. This suggests that gain of function KCNT1 mutations cause epilepsy by increasing resting potassium conductance and suppressing the activity of inhibitory neurons. A reduction in action potential firing in inhibitory neurons due to excessively high resting potassium conductance leads to disinhibition of neural circuits, hyperexcitability and seizures.

TEACHERS' AWARENESS OF DISORDERS IN STUDENTS WITH EPILEPSY

Epilepsy is one of the most common neurological diseases, characterized by recurrent epileptic seizures. Epilepsy can be caused by various factors affecting the brain. Any process affecting the child's brain during its formation leads to insufficient maturation of nerve elements in their morpho-functional structure. Depending on the degree and nature of the brain damage, the location of the lesion, its depth and spread, there are different forms of epilepsy, manifesting themselves in different ways. Disorders accompanying the disease are: attention deficit, neuropsychiatric disorders, motility disorders. Children with epilepsy may have a general intellectual disability (mental retardation), global developmental delay, hearing or vision impairment, autism spectrum disorders and others. The aim of the present study is to research and analyze the awareness of teachers working in educational institutions about the disorders and the presence of learning difficulties in students with epilepsy. The materials and methods used in the study are sociological, documentary and graphical analyses of the results. The study included 133 teachers working in schools in the city of Sofia. Results and discussion: The study found that the largest group of teachers aged 31 to 40 years - 39.10%. About 57% of respondents said that students with epilepsy have an attention deficit, but a large percentage of respondents said that there was a decrease in concentration. The study found that teachers were aware of the disease but did not have enough information about the disorders that accompany epilepsy and the learning difficulties that students with epilepsy may have.

Assessment of burden and segregation profiles of CNVs in patients with epilepsy.

ObjectiveMicrodeletions are associated with different forms of epilepsy but show incomplete penetrance, which is not well understood. We aimed to assess whether unmasked variants or double CNVs could explain incomplete penetrance.MethodsWe analyzed copy number variants (CNVs) in 603 patients with four different subgroups of epilepsy and 945 controls. CNVs were called from genotypes and validated on whole‐genome (WGS) or whole‐exome sequences (WES). CNV burden difference between patients and controls was obtained by fitting a logistic regression. CNV burden was assessed for small and large (>1 Mb) deletions and duplications and for deletions overlapping different gene sets.ResultsLarge deletions were enriched in genetic generalized epilepsies (GGE) compared to controls. We also found enrichment of deletions in epilepsy genes and hotspots for GGE. We did not find truncating or functional variants that could have been unmasked by the deletions. We observed a double CNV hit in two patients. One patient also carried a de novo deletion in the 22q11.2 hotspot.InterpretationWe could corroborate previous findings of an enrichment of large microdeletions and deletions in epilepsy genes in GGE. We could also replicate that microdeletions show incomplete penetrance. However, we could not validate the hypothesis of unmasked variants nor the hypothesis of double CNVs to explain the incomplete penetrance. We found a de novo CNV on 22q11.2 that could be of interest. We also observed GGE families carrying a deletion on 15q13.3 hotspot that could be investigated in the Quebec founder population.

A de novo missense variant in GABRA4 alters receptor function in an epileptic and neurodevelopmental phenotype.

Variants in γ‐aminobutyric acid A (GABAA) receptor genes cause different forms of epilepsy and neurodevelopmental disorders. To date, GABRA4, encoding the α4‐subunit, has not been associated with a monogenic condition. However, preclinical evidence points toward seizure susceptibility. Here, we report a de novo missense variant in GABRA4 (c.899C>T, p.Thr300Ile) in an individual with early‐onset drug‐resistant epilepsy and neurodevelopmental abnormalities. An electrophysiological characterization of the variant, which is located in the pore‐forming domain, shows accelerated desensitization and a lack of seizure‐protective neurosteroid function. In conclusion, our findings strongly suggest an association between de novo variation in GABRA4 and a neurodevelopmental disorder with epilepsy.

Role of the <i>GRIN1</i> gene polymorphism in the formation of post-traumatic epilepsy

Introduction: NMDA receptors are involved in the pathogenesis of seizures, as it subunit is coded for by the GRIN1 gene. Different GRIN1 mutations are known in patients with different forms of epilepsy and encephalopathy. However, no data are available on the participation of the GRIN1 gene and its polymorphisms in the development of post-traumatic epilepsy (PTE). Aim: To determine the influence of single-nucleotide rs1126442 polymorphism of GRIN1 on the risk of PTE formation. Materials and methods: A total of 140 patients were examined, which included 69 patients with PTE and 71 patients with genetic epilepsy. All patients underwent a comprehensive examination, with evaluation of history, neurological status, electroencephalography (EEG) and neuroimaging results, and genotyping of blood samples by real-time polymerase chain reaction. The control sample for genetic examination was venous blood from 60 healthy individuals. Results: Focal seizures with transition to bilateral and tonicclonic seizures were predominant in the PTE group. Neuroimaging revealed dystrophic, cystic, and cystogliotic alterations and signs of external hydrocephaly. EEG recorded interictal and ictal epileptiform activity and slowing of theta waves. Genotyping by rs1126442 polymorphism of GRIN1 revealed predominance of heterozygous G/A and homozygous A/A genotypes in patients with PTE in the codominant (odds ratio (OD)=3.43; 95% confidence index (CI) 1.567.55; p=0.0047), dominant (OR=3.24; 95% CI 1.576.68; p=0.0011), and superdominant (OR=2.90; 95% CI 1.366.22; p=0.0048) inheritance models. The carriage of heterozygous G/A rs1126442 genotype of GRIN1 was associated with an epileptiform activity in the EEG of all patients with epilepsy (OR=2.40; 95% CI 1.115.20; p=0.024). Conclusion: The carriage of heterozygous G/A genotype and homozygous A/A rs 1126442 genotype of GRIN1 in the dominant and codominant inheritance models is associated with a high risk of development of epilepsy after craniocerebral trauma. The carriage of heterozygous G/A rs 1126442 genotype of GRIN1 is associated with an epileptiform activity in EEG.

Effectiveness, safety and assessing the results of drug therapy in patients with epilepsy

On June 26, 2021, a meeting of the experts of the Russian League Against Epilepsy (RLAE) was held, dedicated to the effectiveness, safety and assessing the results of drug therapy in patients with epilepsy. Having considered the history of the issue and guided by domestic and foreign experience, the participants discussed the problems associated with the use of various antiepileptic drugs for different forms of epilepsy in patients of different sex and age. Special attention was paid to psychiatric comorbidity in patients with epilepsy, increasing their compliance with treatment and quality of life. The article presents the Resolution of RLAE experts meeting adopted as a result of the discussion.

Ligand-gated ion channels in genetic disorders and the question of efficacy.

Whole-genome sequencing has unearthed a substantial number of individual variants in ion channels associated with genetic disorders. Ligand-gated ion channels, including glycine, γ-aminobutyric acid type A and nicotinic acetylcholine receptors, have long been known to harbour genetic variants associated with hyperekplexia and different forms of epilepsy. In some of these cases, missense variants enhance or impair the intrinsic ability of the receptor to convert ligand binding to channel opening, or the efficacy of receptor activation. We review the current understanding of how ligand-gated ion channels are activated and the properties that define the efficacy of an agonist, and how these properties can be altered by disease-causing variants. Additionally, we consider the mechanisms defining drug modulation of receptors and consider how this may differ in genetic variants. This fundamental knowledge is likely to be essential in understanding how effective treatments will be for patients with genetic variants in ligand-gated ion channels.

Plant derived versus synthetic cannabidiol: Wishes and commitment of epilepsy patients

PurposeA special component of cannabis, cannabidiol (CBD), is currently in the focus of epilepsy treatment and research. In this context, we investigated patients’ expectations and preferences pertaining to plant-derived versus synthetic formulation of cannabidiol, as well as their willingness to get this treatment. MethodsOne hundred and four of 153 patients with different forms of epilepsy (54 % female, mean age 40 ± 16 yrs.) responded to the survey. The survey consisted of 8 questions addressing expectations of and concerns towards CBD treatment, preferences of plant-derived versus synthetic CBD, estimated monthly costs, and willingness to buy CBD at one’s own expense. ResultsThe majority (73 %) of the responding epilepsy patients wished to receive plant-derived CBD; 5 % preferred synthetic CBD. Reasons for this choice were botanic origin, lack of chemistry, and the assumption of fewer and less dangerous side effects. Eighty-two percent of the patients estimated the monthly costs of CBD treatment to be below €500. Using the willingness-to-pay approach to assess the commitment of patients, 68 % could imagine buying the drug themselves. Fifty-three percent of these would be willing to pay up to €100, 40 % €100 to €200, and another 7 % €200 to €500 per month. ConclusionThere is an overwhelming preference towards plant-derived cannabidiol in epilepsy patients, driven by the idea of organic substances being safer and better tolerated than synthetic. The willingness-to-pay approach reflects the high burden and pressure of uncontrolled epilepsy and the expectation of relief. Non-realistic ideas of pricing as well as what patients would be willing and able to pay confirm this perception.

Comparative analysis of zonisamide and topiramate use in treatment of pediatric epilepsy in real clinical practice: the results of a retrospective study and related clinical cases

Background. Comparative study of antiepileptic drugs allows to make the optimal choice in therapy.The aim of the study: a comparative analysis of the administration of two similar by chemical structure antiepileptic drugs (zonisamide and topiramate) in the outpatient practice in epilepsy in children, taking into account the efficacy and tolerability.Materials and methods. A retrospective analysis of outpatient charts of equal in number (n = 18) groups of patients with different forms of epilepsy treated with zonisamide and topiramate in monotherapy and in combined therapy was carried out.Results. In general, no statistically significant difference in the efficacy of zonisamide and topiramate was obtained (p = 0.692). Efficacy in structural focal epilepsy was also comparable (absence of seizures 54.6 % and 45.5 %, respectively). With comparable efficacy, zonisamide was administered to patients much later in the antiepileptic drugs (Me = 5) than topiramate (Me = 3). Side effects on zonisamide were registered in 27.8 %, side effects on topiramate – in 38.9 % (p = 0.480). The difference in the effect of these drugs on cognitive functions was noted.Conclusions. Zonisamide shows its effectiveness in different forms of epilepsy in children, despite the later appointment in practice. The drug is well tolerated and probably has less negative effect on children’s cognitive functions than topiramate.

Safe and sound: Meta-analyzing the Mozart effect on epilepsy

ObjectiveThe use of music-based neuro-stimulation for treating seizures and interictal epileptiform discharges (IED) (the so-called “Mozart effect”) remains a controversial issue. We have conducted an updated meta-analysis in order to systematically review literature evidence and provide further insights about the role of the Mozart effect in epilepsy. MethodsFollowing the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” (PRISMA) guidelines, we searched three bibliographic databases from their date of inception to January 2020. Nine meta-analyses were performed according to both music stimulation protocols and outcome measures. We applied the Cochrane Q-test and the I2-index for heterogeneity evaluation, and either fixed-effect or random-effect models to compute mean differences and pool data. ResultsOf 147 abstracts, 12 studies were included and grouped according to stimulation protocols and outcome measures. The nine meta-analyses showed significant reductions in seizures and IED frequencies after long-term music treatment, and in IED frequency during and after a single music stimulus. ConclusionsMusic-based neurostimulation may improve the clinical outcome of individuals with epilepsy, by reducing the frequency of seizures and IED. Further and stronger evidence will allow defining its potential in the different forms of epilepsy, and the most effective stimulation protocols. SignificanceMusic therapy should be considered as a complementary, non-invasive approach for treating epilepsy and epileptiform discharges.

Cognitive impairment in children with epilepsy

Introduction. Epilepsy makes its debut in childhood and adolescence, being one of the main diseases in pediatric neurology. Epilepsy in children can often lead to significant cognitive disorders.
 The purpose of the work is to identify the features of mental and cognitive development of children with epilepsy.
 Material and methods. A group of 929 children aged 2-11 years with different forms of epilepsy was examined. Depending on the age and severity of the disease, the children underwent a complete neuropsychological examination with in-depth study of verbal-mnestic and speech functions, or a survey based on a specially developed mental development profile for children with mental disabilities. For children with preserved intelligence, the method of syndrome analysis was adapted and applied. Based on the results of testing, qualitative and quantitative assessment of the parameters of the analyzed processes was carried out. The mental development profile for the child was displayed graphically, with the introduction of quantitative and qualitative assessments of certain areas of cognitive activity. Electrophysiological, neuroimaging and standard clinical diagnostic methods were used in all children.
 Results. The specificity of neuropsychological deficiency in children with epilepsy is determined by the locus of epiactivity. The peculiarity of the deviant type of formation of mental functions is manifested in children already at the early stages of epilepsy, it is associated with dysfunction of different brain zones due to the negative impact of epileptiform activity.
 Neuropsychological syndromes in different forms of epilepsy are variable, their psychological content is determined by factors related to the localization of the focus of epiactivity, the childs mental development, and the severity of the disease.
 The interhemispheric asymmetry of neuropsychological deficits was established for different locations of the epiactivity focus. The greatest severity of cognitive impairment is observed when the focus is located in the left hemisphere. The location of the epicenter of epiactivity in the frontotemporal regions can lead to cerebral dementia (the collapse of simple programs and purposeful subject activity), and behavior disorders.
 Children with epilepsy who have an epiactivity locus in the parietal-occipital regions of the brain have violations of constructive praxis and visual-spatial gnosis, as well as difficulties in learning to read and write.
 Conclusion. The neuropsychological method of studying the structural and functional foundations of mnestic, speech, and other types of cognitive activity in children with epilepsy has allowed us to establish that deviations in the development of mental functions in this category of children arise from insufficiently formed individual links of the functional system and the relationship between them. The presence of an epicenter of epilepsy in children with epilepsy at the early stages of the disease can cause a neuropsychological deficit in the development of higher mental functions.

A novel de novo variant of GABRA1 causes increased sensitivity for GABA in vitro

The GABRA1 gene encodes one of the most conserved and highly expressed subunits of the GABAA receptor family. Variants in this gene are causatively implicated in different forms of epilepsy and also more severe epilepsy-related neurodevelopmental syndromes. Here we study functional consequences of a novel de novo missense GABRA1 variant, p.(Ala332Val), identified through exome sequencing in an individual affected by early-onset syndromic epileptic encephalopathy. The variant is localised within the transmembrane domain helix 3 (TM3) and in silico prediction algorithms suggested this variant to be likely pathogenic. In vitro assessment revealed unchanged protein levels, regular assembly and forward trafficking to the cell surface. On the functional level a significant left shift of the apparent GABA potency in two-electrode voltage clamp electrophysiology experiments was observed, as well as changes in the extent of desensitization. Additionally, apparent diazepam potency was left shifted in radioligand displacement assays. During prenatal development mainly alpha2/3 subunits are expressed, whereas after birth a switch to alpha1 occurs. The expression of alpha1 in humans is upregulated during the first years. Thus, the molecular change of function reported here supports pathogenicity and could explain early-onset of seizures in the affected individual.

Epilepsy Benchmarks Area III: Improved Treatment Options for Controlling Seizures and Epilepsy-Related Conditions Without Side Effects.

The goals of Epilepsy Benchmark Area III involve identifying areas that are ripe for progress in terms of controlling seizures and patient symptoms in light of the most recent advances in both basic and clinical research. These goals were developed with an emphasis on potential new therapeutic strategies that will reduce seizure burden and improve quality of life for patients with epilepsy. In particular, we continue to support the proposition that a better understanding of how seizures are initiated, propagated, and terminated in different forms of epilepsy is central to enabling new approaches to treatment, including pharmacological as well as surgical and device-oriented approaches. The stubbornly high rate of treatment-resistant epilepsy—one-third of patients—emphasizes the urgent need for new therapeutic strategies, including pharmacological, procedural, device linked, and genetic. The development of new approaches can be advanced by better animal models of seizure initiation that represent salient features of human epilepsy, as well as humanized models such as induced pluripotent stem cells and organoids. The rapid advances in genetic understanding of a subset of epilepsies provide a path to new and direct patient-relevant cellular and animal models, which could catalyze conceptualization of new treatments that may be broadly applicable across multiple forms of epilepsies beyond those arising from variation in a single gene. Remarkable advances in machine learning algorithms and miniaturization of devices and increases in computational power together provide an enhanced opportunity to detect and mitigate seizures in real time via devices that interrupt electrical activity directly or administer effective pharmaceuticals. Each of these potential areas for advance will be discussed in turn.

The Effect of Seizures on Sleep and Behavior in Children

Children with seizures experience a wide range of different problems that are a result of their different forms of epilepsy. Some problems children experience are sleep disturbances, behavior issues or mood swings, social problems and poor academic performance. The severity of these problems that each individual child may experience is dependent upon the locations of the seizures and the child themselves.

Use of Cannabidiol in the Treatment of Epilepsy: Efficacy and Security in Clinical Trials.

Cannabidiol (CBD) is one of the cannabinoids with non-psychotropic action, extracted from Cannabis sativa. CBD is a terpenophenol and it has received a great scientific interest thanks to its medical applications. This compound showed efficacy as anti-seizure, antipsychotic, neuroprotective, antidepressant and anxiolytic. The neuroprotective activity appears linked to its excellent anti-inflammatory and antioxidant properties. The purpose of this paper is to evaluate the use of CBD, in addition to common anti-epileptic drugs, in the severe treatment-resistant epilepsy through an overview of recent literature and clinical trials aimed to study the effects of the CBD treatment in different forms of epilepsy. The results of scientific studies obtained so far the use of CBD in clinical applications could represent hope for patients who are resistant to all conventional anti-epileptic drugs.

ANALYSIS OF CANDIDATE POLYMORPHISMS AT EPILEPSY PATIENTS WITHOUT MECHANICAL DISTURBANCES

Thе article presents the results of a molecular-genetics research on patients with diagnosed epilepsy without mechanical disturbance. The aim of this research was the analysis of candidate gene polymorphisms in development of different forms of epilepsy excepting mechanical reasons. 78 patients of V.M. Savinov SVS clinic with different forms of epilepsy were selected for the molecular-genetic analysis. Genotyping on candidate polimorphisms of gene coding the methyl-СрG-binding protein 2 (МЕСР2, 3 polymorphisms), the genes of sodium (SCN1A, 4 polymorphisms) and potassium (KCNT1, 2 polymorphisms) channels was performed by a site-specific PCR-RFLP method. Molecular genetic analysis revealed the presence of normal functioning alleles for 3 investigated candidate polymorphisms (p.Thr158Met, p.Thr197Met, p.Arg306Ter) of 3d exon of МЕСР2 gene at all epilepsy patients. However, 1 case (patient suffering from Dravet syndrome) of de novo mutation was defined for sodium channel gene (SCN1A p.Ala1783Thr) and 3 cases (2 patients suffering from temporal epilepsy and 1 patient with residual encephalopathy) of new mutations in gene responsible for potassium channel (KCNT1 p.Ala934Thr). To determine the inherited SCN1A and KCNT1 mutations, the molecular-genetics analysis was conducted for close relatives of patients. As a result, we conclude that, candidate polymorphisms of SCN1A p.Ala1783Thr and KCNT1 p.Ala934Thr, disrupting the ion channels normal functioning, can be involved in development of non-mechanical forms of epilepsy.