Different Types Of Epilepsy Research Articles

ASSOCIATION BETWEEN APOLIPOPROTEIN E POLYMORPHISMS AND EPILEPSY IN CHILDREN.

SUMMARYApolipoprotein E (APOE) plays an important role in lipid metabolism and is a proven risk factor for development of dementia and other neurodegenerative diseases. The aim of the study was to determine the possible connection between particular APOE alleles, blood lipid profile and different types of epilepsy in children. Alleles of the APOE gene, blood cholesterol (total, high-density lipoprotein and low-density lipoprotein (LDL) cholesterol, and triglyceride levels were analyzed in blood samples of 111 children with epilepsy and 118 age- and sex-matched children without epilepsy. Distribution of APOE genotypes was the same in children of both groups. Significantly increased levels of total cholesterol and LDL cholesterol were found in control group (Z=3.49 and 3.52 respectively, p<0.01). No statistically significant difference was found between the genotypes of children with idiopathic and symptomatic epilepsy (χ2=1.96; df=2; p>0.05). There were statistically significant differences in the levels of total cholesterol (Z=2.09; p<0.05) and LDL cholesterol (Z=2.05; p<0.05) according to the type of epilepsy in favor of symptomatic epilepsy. The study confirmed that there was no connection between APOE and type of epilepsy in children and showed the children with epilepsy to have lower total cholesterol and LDL cholesterol levels. Interestingly, this also held true for children with idiopathic epilepsy compared to those with symptomatic condition.

Comparison of screening tests in the evaluation of cognitive status of patients with epilepsy.

ABSTRACT.Epilepsy, a chronic neurological condition which is associated with neurobiological and psychosocial changes, affects 0.5 to 1% of the world's population, presenting in most cases a deficit in reasoning, memory and attention.Objective:To contribute to the implementation of screening strategies for cognitive decline and memory deficits in patients with epilepsy.Methods:Two questionnaires, MMSE and MoCA, were used in this cross-sectional and observational study. Fifty-four patients diagnosed with different types of epilepsy (55% refractory) were assessed; they were all over 18 years old, of both genders, with autonomy to answer the questionnaire. They were followed exclusively at an outpatient clinic of the Neurology Service Department, specialized in epilepsy, which is part of the tertiary healthcare level of the Brazilian Unified Health System (SUS).Results:The final sample consisted of 54 patients. There was a significant correlation (p<0.001) between the scores of both tests, indicating that low values in the MMSE score also corresponded to low values in the MoCA score. Sensitivity was 90% (ROC curve adjusted) and 87.5% of the patients with a normal score in the MMSE test obtained alterations in the MoCA scores. None of them showed a low MMSE score with a normal MOCA score. The Spearman correlation coefficient was 0.80. Also, there was a significant relationship between both immediate memory and delayed recall memory and the type of seizure (p<0.03) and level of schooling (p<0.001), respectively.Conclusion:The MoCA is a well-suited test to be performed in epilepsy patients to evaluate their cognition as it seems more extensive and complete compared to MMSE.

Epileptologists telling their experiences caring for patients with epilepsy

ObjectiveThis research was focused on expert professionals in epilepsy care to understand their points of view on the care pathway and their living relationships with patients. MethodsResearchers prepared a semi-structured parallel chart and distributed it online among 21 Italian centres of care. Each health professional was prompted to write five narratives on cases of patients with epilepsy, subsequently analysed through narrative medicine methods. Next, a consensus meeting was held, to individualise an action plan based on the narratives. ResultsNinety-one parallel charts were collected from 25 epileptologists, who had a mean age of 50 years; their narratives concerned patients with a mean age of 37 years, with different types of epilepsy (53 % drug-resistant; 31 % unemployed). The limitations in the daily life of people with epilepsy (57 %), employment (42 %), caregiver burden (51 %), and the universal prevalence of fear were the primary topics that emerged. Attentive and reassuring care relationships were found to be the main element of coping (21 %). A new multi-factorial classification of epilepsies, integrating clinical with social and legal risk factors, was the main agreed action to face the issues identified. ConclusionsThe narrative medicine approach supplied a broader scenario of living with epilepsy, including the family and social impact and possible effects on the choices for care pathways. The epileptologists showed a strong motivation to care for patients with epilepsy and deep involvement in the care relationships; the use of parallel chart demonstrated to be an effective tool to preserve their wellbeing.

In Vitro and In Vivo Study of the Short-Term Vasomotor Response during Epileptic Seizures.

Epilepsy remains one of the most common brain disorders, and the different types of epilepsy encompass a wide variety of physiological manifestations. Clinical and preclinical findings indicate that cerebral blood flow is usually focally increased at seizure onset, shortly after the beginning of ictal events. Nevertheless, many questions remain about the relationship between vasomotor changes in the epileptic foci and the epileptic behavior of neurons and astrocytes. To study this relationship, we performed a series of in vitro and in vivo experiments using the 4-aminopyridine model of epileptic seizures. It was found that in vitro pathological synchronization of neurons and the depolarization of astrocytes is accompanied by rapid short-term vasoconstriction, while in vivo vasodilation during the seizure prevails. We suggest that vasomotor activity during epileptic seizures is a correlate of the complex, self-sustained response that includes neuronal and astrocytic oscillations, and that underlies the clinical presentation of epilepsy.

Prediction and detection of human epileptic seizures based on SIFT-MS chemometric data

Although epilepsy is considered a public health issue, the burden imposed by the unpredictability of seizures is mainly borne by the patients. Predicting seizures based on electroencephalography has had mixed success, and the idiosyncratic character of epilepsy makes a single method of detection or prediction for all patients almost impossible. To address this problem, we demonstrate herein that epileptic seizures can not only be detected by global chemometric analysis of data from selected ion flow tube mass spectrometry but also that a simple mathematical model makes it possible to predict these seizures (by up to 4 h 37 min in advance with 92% and 75% of samples correctly classified in training and leave-one-out-cross-validation, respectively). These findings should stimulate the development of non-invasive applications (e.g., electronic nose) for different types of epilepsy and thereby decrease of the unpredictability of epileptic seizures.

Clinical profile of children with epilepsy: a cross-sectional study

Introduction: One of the most common chronic neurological disorders is epilepsy, affecting as many as 45 million individuals worldwide. The occurrence is higher in children below the age of three. Around 60 percent to 70 percent of epilepsy patients have an effective response to treatment with antiepileptic medications. This cross-sectional study aimed to explore the clinical profile of children with epilepsy.Methods: Total of 100 children with different types of epilepsy was included in this study. After getting informed consent from the parents, all the demographic data, family history, clinical and laboratory investigations were recorded, and the results were statistically analyzed and discussed.Results: 69 patients had tonic-clonic seizures, 15 patients had a complete partial seizure, 7 patients had absence seizures, 4 patients had unclassified seizures, 3 patients had simple partial seizures, 1 patient had myoclonic seizures, atonic seizures and multiple seizures. Aetiology, 72 patients had an idiopathic cause, 10 patients had hypoxic ischemia, 8 patients had Central nervous system (CNS) infection, 4 patients had cerebral palsy and space-occupying lesion, 2 patients had trauma. Comorbidity, 84 patients had none, 4 patients had mental retardation, 3 patients had eye diseases, cerebral palsy, protein-energy malnutrition, mental retardation with cerebral palsy, 1 patient had a hearing impairment. Drug therapy, 63 patients had sodium valproate, 11 patients had carbamazepine, 2 patients had multidrug treatment, and 1 patient had sodium phenytoin.Conclusion: A significant amount of the aetiology of the condition is expressed among preventable causes of epilepsy. For generalized tonic clonic seizure, sodium valproate was observed to have more positive effects in paediatric patients.

S3437 Antibiotic Therapy Followed by Faecal Microbiota Transplantation Alleviates Epilepsy – A Case Report

INTRODUCTION: Epilepsy is a neurological disorder characterised by recurrent seizures which are caused by a temporary disruption of electrical activity in the brain. There are many different types of epilepsy and people’s experiences differ greatly. Epilepsy can start at any age although it is more likely to be diagnosed in childhood. Half of the causes of epilepsy are still unknown. One hypothesis is that epilepsy may be due to dysbiosis of the gastrointestinal microbiome and molecules generated there subsequently influence the gut-brain-axis. CASE DESCRIPTION/METHODS: Our case is a 33-year-old male patient who has a long history of seizures and gastrointestinal problems, treated at our institute since 2011. He was diagnosed with epilepsy at the age of five after having approximately five seizures per day. Treatment with anticonvulsants was exhaustive as he had both single and combination drug dosages to maximal levels from age 5 to 17 years. Investigation for surgical intervention was proposed to which he refused to consent. At the age of six, he had stomach pains and sleep disturbances which led to diagnosis of ileitis and sleep apnoea. He was commenced on Continuous positive airway pressure for sleep apnoea but discontinued due to lack of improvement. At the same time, he had “gut feelings” with confusion like sensations 2-7 times/day and sleepiness which led to diagnosis of reactive hypoglycaemia and insulin resistance. He presented to our institute for treatment for ileitis. He was assessed and prescribed antibiotics. At the time that antibiotic treatment was commenced, he was sleeping in his mother’s room as convulsions were occurring every 2 hours from 3am to 9am with abnormal breathing noted ahead of time. On the first night after antibiotic treatment commenced, his breathing became regular and interestingly he could be moved back to his own bedroom. Extraordinarily, his sleep apnoea ceased, and seizures reduced in frequency and severity. He was then treated with Faecal Microbiota transplantation (FMT) via rectal enema followed by oral FMT capsules which further reduced seizures (no full seizures for 3-4 months) and “gut feelings” in frequency and improved his quality of life. DISCUSSION: This case indicates that antibiotics and FMT treatment may be effective in alleviating epilepsy symptoms. It also provides further evidence of possible gut dysbiosis as a contributing factor to the pathogenesis of epilepsy.

Vitexin Possesses Anticonvulsant and Anxiolytic-Like Effects in Murine Animal Models.

Different types of epilepsy and forms of pathological anxiety have been described as significant neurological disorders that may exist as comorbidities. Some of those disorders share the association of affected limbic areas/neuropathological triggers as well as the use of drugs for their clinical management. The aim of this work was to investigate the anticonvulsant and anxiolytic properties of the vitexin (apigenin-8-C-glucoside), since this compound is a flavonoid usually found as one of the major constituents in several medicinal plants claimed as anxiolytics and/or anticonvulsants. This investigation was performed by the use of a series of classical murine animal models of chemically induced-seizures and of anxiety-related tests (open-field, elevated plus-maze, and light-dark box tests). Here, we show that the systemic administration of vitexin (1.25; 2.5 and 5 mg/kg; i.p.) exhibited selective protection against chemically-induced seizures. Vitexin did not block seizures evoked by glutamate receptors agonists (NMDA and kainic acid), and it did not interfere with the latencies for these seizures. Conversely, the same treatments protected the animals in a dose-dependent manner against the seizures evoked by the Gabaergic antagonists picrotoxin and PTZ and rise the latency time for the first seizure on non-protected animals. The higher dose of vitexin protected 100% of animals against the tonic-clonic seizures triggered by GABA antagonists. The results from open-field, elevated plus-maze, and light-dark box tests indicated the anxiolytic properties of vitexin at similar range of doses described for the anticonvulsant action screening. Furthermore, these results pointed that vitexin did not cause sedation or locomotor impairment on animals. The selective action of vitexin against picrotoxin and PTZ may reinforce the hypothesis by which this compound acts mainly by the modulation of GABAergic neurotransmission and/or related pathways. This could be useful to explain the dual activity of vitexin as anticonvulsant and anxiolytic, and highlight the pharmacological interest on this promising flavonoid.

Novel and de novo point and large microdeletion mutation in PRRT2-related epilepsy.

BackgroundPoint and copy number variant mutations in the PRRT2 gene have been identified in a variety of paroxysmal disorders and different types of epilepsy. In this study, we analyzed the phenotypes and PRRT2‐related mutations in Chinese epilepsy children.MethodsA total of 492 children with epilepsy were analyzed by whole exome sequencing (WES) and low‐coverage massively parallel CNV sequencing (CNV‐seq) to find the single nucleotide variants and copy number variations (CNVs). And quantitative polymerase chain reaction was utilized to verify the CNVs. Their clinical information was followed up.ResultsWe found PRRT2‐related mutations in 19 patients (10 males and nine females, six sporadic cases and 13 family cases). Twelve point mutations, four whole gene deletion, and three 16p11.2 deletions were detected. The clinical features of 39 patients in 19 families included one early childhood myoclonic epilepsy (ECME), one febrile seizure (FS), two infantile convulsions with paroxysmal choreoathetosis (ICCA), six paroxysmal kinesigenic dyskinesias (PKD), 12 benign infantile epilepsy (BIE), and 17 benign familial infantile epilepsy (BFIE). All patients had normal brain MRI. Interictal EEG showed only one patient had generalized polyspike wave and five patients had focal transient discharges. Focal seizures originating in the frontal region were recorded in one patient, two from the temporal region, and two from the occipital region. Most patients were treated effectively with VPA or OXC, and the child with myoclonic seizures was not sensitive to antiepileptic drugs.Conclusion PRRT2 mutations can be inherited or de novo, mainly inherited. The clinical spectrum of PRRT2 mutation includes BIE, BFIE, ICCA, PKD, FS, and ECME. The PRRT2‐related mutations contained point mutation, whole gene deletion and 16p11.2 deletions, and large microdeletion mutations mostly de novo. It is the first report of PRRT2 mutation found in ECME. Our report expands the mutation and clinical spectrum of PRRT2‐related epilepsy.

Analysis of gene variants in the GASH/Sal model of epilepsy

Epilepsy is a complex neurological disorder characterized by sudden and recurrent seizures, which are caused by various factors, including genetic abnormalities. Several animal models of epilepsy mimic the different symptoms of this disorder. In particular, the genetic audiogenic seizure hamster from Salamanca (GASH/Sal) animals exhibit sound-induced seizures similar to the generalized tonic seizures observed in epileptic patients. However, the genetic alterations underlying the audiogenic seizure susceptibility of the GASH/Sal model remain unknown. In addition, gene variations in the GASH/Sal might have a close resemblance with those described in humans with epilepsy, which is a prerequisite for any new preclinical studies that target genetic abnormalities. Here, we performed whole exome sequencing (WES) in GASH/Sal animals and their corresponding controls to identify and characterize the mutational landscape of the GASH/Sal strain. After filtering the results, moderate- and high-impact variants were validated by Sanger sequencing, assessing the possible impact of the mutations by “in silico” reconstruction of the encoded proteins and analyzing their corresponding biological pathways. Lastly, we quantified gene expression levels by RT-qPCR. In the GASH/Sal model, WES showed the presence of 342 variations, in which 21 were classified as high-impact mutations. After a full bioinformatics analysis to highlight the high quality and reliable variants, the presence of 3 high-impact and 15 moderate-impact variants were identified. Gene expression analysis of the high-impact variants of Asb14 (ankyrin repeat and SOCS Box Containing 14), Msh3 (MutS Homolog 3) and Arhgef38 (Rho Guanine Nucleotide Exchange Factor 38) genes showed a higher expression in the GASH/Sal than in control hamsters. In silico analysis of the functional consequences indicated that those mutations in the three encoded proteins would have severe functional alterations. By functional analysis of the variants, we detected 44 significantly enriched pathways, including the glutamatergic synapse pathway. The data show three high-impact mutations with a major impact on the function of the proteins encoded by these genes, although no mutation in these three genes has been associated with some type of epilepsy until now. Furthermore, GASH/Sal animals also showed gene variants associated with different types of epilepsy that has been extensively documented, as well as mutations in other genes that encode proteins with functions related to neuronal excitability, which could be implied in the phenotype of the GASH/Sal. Our findings provide valuable genetic and biological pathway data associated to the genetic burden of the audiogenic seizure susceptibility and reinforce the need to validate the role of each key mutation in the phenotype of the GASH/Sal model.

How to interpret images in epileptic seizures: correlation between clinical and functional MRI findings

Neuroimaging studies are essential in patients with epilepsy, both for diagnosis and surgical management. This article focuses on adult epileptic patients, reviewing the updated clinical criteria published by the International League Against Epilepsy for the definitions of seizures, epilepsy, and status epilepticus. It also describes the different types of epilepsy, the different presentations, the signs, the radiologic approach to managing seizures, and the differences between generalized and focal seizures. Finally, it discusses the relations between possible functional cerebral deficits secondary to potentially epileptogenic lesions and epilepsy surgery, underlining the importance of functional magnetic resonance imaging studies.

Clinical evaluation of psychiatric and behavioral disorders in adolescents with epilepsy: a cross-sectional study

Background: Epilepsy is a neurological disease that is often associated with psychiatric comorbidities.Subjects and methods: The aim of the study was to examine the frequency of psychic symptoms and their association with different types of epilepsy in the adolescent population. The study involved 100 adolescents with epilepsy and 100 healthy adolescents of both sexes at the age of 13–19. The examinees completed a standardized Symptom Checklist-90-R (SCL-90-R) questionnaire, concerning self-assessment of psychological disorders in the previous week. The value system of ​​nine dimensions and three global indexes of SCL-90-R scales were analyzed.Results: Our results suggest that adolescents with epilepsy have more than one psychic disorder compared to a healthy group of respondents. Somatic symptoms are more common in non-epileptic subjects, while obsessive-compulsive, depressive and phobic symptoms, as well as anxiety, aggressiveness, interpersonal vulnerability and paranoia, are more common in adolescents with epilepsy. Due to the type of epilepsy, obsessive compulsive symptoms are more common in adolescents with focal epilepsy, while the symptoms of phobia are more present in those with generalized epilepsy. The depth and intensity of psychological stress is higher in the group of adolescents with epilepsy compared to the healthy group of respondents.Conclusions: Psychiatric comorbidity is very common in epileptic patients and depending on the type of diagnosed epilepsy, various symptoms are expressed. Furthermore, psychological stress is more observable in adolescents with epilepsy. For patients with epilepsy, mental health care and seizure control is extremely important in the prevention of serious mental disabilities.

Comparisons of direct and indirect utilities in adult epilepsy populations: A systematic review

Epilepsy is common and carries substantial morbidity, and therefore identifying cost-effective health interventions is essential. Cost-utility analysis is a widely used method for such analyses. For this, health conditions are rated in terms of utilities, which provide a standardized score to reflect quality of life. Utilities are obtained either indirectly using quality of life questionnaires, or directly from patients or the general population. We sought to describe instruments used to estimate utilities in epilepsy populations, and how results differ according to methods used. We undertook a systematic review of studies comparing at least two instruments for obtaining utilities in epilepsy populations. MEDLINE, Embase, ScienceDirect, Cochrane Library, Google Scholar, and gray literature were searched from inception to June 2019. Mean utilities were recorded and compared for each method. Of the 38 unique records initially identified, eight studies met inclusion criteria. Utilities were highest for direct "tradeoff" methods, obtained via instruments including standard gamble (0.93) and time tradeoff (0.92), compared to indirect methods, obtained via instruments including EuroQoL five-dimensional form (range = 0.72-0.86) and Health Utilities Index Mark 3 (range = 0.52-0.71). Visual analog scale (VAS), a direct "nontradeoff" instrument, provided equal or lower utilities (range = 68.0-79.8) compared to indirect instruments. Direct methods, with the important exception of VAS, may provide higher utilities than indirect methods. More studies are needed to identify the most appropriate utility instruments for epilepsy populations, and to investigate whether there is variation between utilities for different types of epilepsy and other patient- and disease-specific factors.

Crisis epiléptica: ¿cómo interpretar la imagen? Correlación clínica-funcional

Neuroimaging studies are essential in patients with epilepsy, both for diagnosis and surgical management. This article focuses on adult epileptic patients, reviewing the updated clinical criteria published by the International League Against Epilepsy for the definitions of seizures, epilepsy, and status epilepticus. It also describes the different types of epilepsy, the different presentations, the signs, the radiologic approach to managing seizures, and the differences between generalized and focal seizures. Finally, it discusses the relations between possible functional cerebral deficits secondary to potentially epileptogenic lesions and epilepsy surgery, underlining the importance of functional magnetic resonance imaging studies.

Depression and situational anxiety are risk factors for noncompliance with medical treatment in adult patients with epilepsy in Kyrgyzstan

To determine the severity of depression and anxiety in patients with different types of epilepsy, not treated with antidepressive drugs and anxiolytics and to make a correlation with antiepileptic drugs compliance. A case-control study was done in Kyrgyzstan, Bishkek City Clinic 1, in the group of interest patients with long term of all types of epilepsy were included and in control group we enrolled other neurological patients, free from seizures and epilepsy. We used clinical diagnosis of epilepsy, confirmed with EEG findings. Zung depression scale and Spilberger scale for the anxiety diagnostics were adapted to Kyrgyz language and applied. 65 patients were included in the study: 34 were with epilepsy. Of the total sample nearly 70.0% of participants had anxiety and 61% in epilepsy group. The most prevalent symptom of anxiety was “the expecting of seizures";” (67.6%). We found strong correlation between low educational level and the risk of pills withdrawal: (OR = 2.79, 95% CI = 1.04–3.05), but higher education was the risk for anxiety (OR = 3.1, 95% CI = 2.15–4.01). Patients using benzodiazepins were prone to withdraw it in long term more due to side effects (45%), compared to valproate group (11%). 28% patients with epilepsy were prone to withdraw pills due to moderate depression (OR = 4.35, 95% CI = 2.27–8.31). High level of situational anxiety and moderate level of depression were associated with lower compliance to antiepileptic regimen. Patients in Kyrgyzstan tend to adhere to pursuing alternative regimens (traditional medicine).

An Italian multicentre study of perampanel in progressive myoclonus epilepsies

Perampanel (PER) is a novel anti-seizure medication useful in different types of epilepsy. We intended to assess the effectiveness of PER on cortical myoclonus and seizure frequency in patients with progressive myoclonus epilepsy (PME), using quantitative validated scales.Forty-nine patients aged 36.6 ± 15.6 years with PME of various aetiology (18 EPM1, 12 EPM2, five with sialidosis, one with Kufs disease, one with EPM7, and 12 undetermined) were enrolled between January 2017 and June 2018. PER at the dose of 2–12 mg (5.3 ± 2.5) was added to existing therapy. Myoclonus severity was assessed using a minimal myoclonus scale (MMS) in all the patients before and after 4–6 months of steady PER dose, and by means of the Unified Myoclonus Rating Scale (UMRS) in 20 patients. Logistic regression analysis was used to identify the factors potentially predicting treatment efficacy.Four patients dropped out in the first two months due to psychiatric side effects. In the remaining patients, PER reduced myoclonus severity as assessed using MMS (Wilcoxon test: p < 0.001) and UMRS (p < 0.001), with the ‘Action myoclonus’ section of the UMRS showing the greatest improvement. The patients with EPM1 or EPM1-like phenotype were more likely to improve with PER (p = 0.011). Convulsive seizures which have recurred at least monthly in 17 patients were reduced by >50%. Side effects occurred in 22/49 (44.8%) patients, the most common being irritability followed by drowsiness.PER is effective in treating myoclonus and seizures in PME patients. The frequency of psychiatric side effects suggests the need for careful patient monitoring.

Uterine epilepsy: a historical report from Avicenna's point of view.

Epilepsy is a common neurological disorder, the history of which dates back to thousands of years ago. Avicenna (980-1037 AD) is a famous Persian scholar who considered different types of epilepsy and their specific treatments. His book Al-Qanun fi al-Tibb was taught in Europe for several years. Along with explaining the diseases occurring in various body organs, the book describes neurological and neuropsychological conditions such as epilepsy METHODS: This article is a review of the book Al-Qanun fi al-Tibb and some of the traditional Persian medicine sources, including Kāmil al-Sināa al Tibbiya and Makhzan-O-L Advieh, on uterine epilepsy, its etiology, clinical manifestations and treatments. Also, articles related to this topic in the field of traditional Persian medicine or historical articles have been searched for in Google Scholar search engine or PubMed database. Avicenna categorizes the causes of epilepsy into two main groups: those caused by brain diseases and those associated with the diseases of other organs. He believed that the stomach, the spleen, the maraqq, the uterus, or other body organs influence the brain and can cause epilepsy. In uterine epilepsy, the primary pathology lies with the uterus and can affect the brain. This condition occurs due to the retention of the menses or semen. In this historical article, we intend to explain Avicenna's viewpoint on uterine epilepsy. We suggest further studies on this topic, for example, to evaluate the frequency of epilepsy in patients with the retention of the menses or the semen.

Ultra-Rare Genetic Variation in the Epilepsies: A Whole-Exome Sequencing Study of 17,606 Individuals

Sequencing-based studies have identified novel risk genes associated with severe epilepsies and revealed an excess of rare deleterious variation in less-severe forms of epilepsy. To identify the shared and distinct ultra-rare genetic risk factors for different types of epilepsies, we performed a whole-exome sequencing (WES) analysis of 9,170 epilepsy-affected individuals and 8,436 controls of European ancestry. We focused on three phenotypic groups: severe developmental and epileptic encephalopathies (DEEs), genetic generalized epilepsy (GGE), and non-acquired focal epilepsy (NAFE). We observed that compared to controls, individuals with any type of epilepsy carried an excess of ultra-rare, deleterious variants in constrained genes and in genes previously associated with epilepsy; we saw the strongest enrichment in individuals with DEEs and the least strong in individuals with NAFE. Moreover, we found that inhibitory GABAA receptor genes were enriched for missense variants across all three classes of epilepsy, whereas no enrichment was seen in excitatory receptor genes. The larger gene groups for the GABAergic pathway or cation channels also showed a significant mutational burden in DEEs and GGE. Although no single gene surpassed exome-wide significance among individuals with GGE or NAFE, highly constrained genes and genes encoding ion channels were among the lead associations; such genes included CACNA1G, EEF1A2, and GABRG2 for GGE and LGI1, TRIM3, and GABRG2 for NAFE. Our study, the largest epilepsy WES study to date, confirms a convergence in the genetics of severe and less-severe epilepsies associated with ultra-rare coding variation, and it highlights a ubiquitous role for GABAergic inhibition in epilepsy etiology.

Sociodemographic, Rationale Drug Use of Antiepileptic Drugs among Pediatric Patients with Epilepsy: A Prospective Study at a Tertiary Care Hospital.

Background Drug utilization studies are important and considered as a potential tool for the evaluation of health care systems. The goal of drug utilization research studies should be to assess whether drug therapy is rational or not. Objective The main aim of this article is to analyze the different types of epilepsy and their drug utilization pattern in children with epilepsy at the Department of Pediatrics and evaluate the extent of older and newer antiepileptic drugs (AEDs), either as monotherapy or polytherapy in pediatric age groups. Materials and Methods To look into the sociodemographic profile of children with epilepsy, the type of epilepsy was diagnosed along with drug utilization pattern in children attending both outpatient and inpatient department of pediatrics. Demographic details were collected according to modified Kuppuswamy scale. Disease characteristics such as type of epilepsy, onset, duration, time since last attack, family history, comorbid conditions, monotherapy/polytherapy, dose, and duration of treatment were noted. Investigations such as electroencephalography, magnetic resonance imaging, and computed tomographic scan if any were recorded. Results In this pilot study, we have 100 patients, younger than 18 years, with confirmed cases of epilepsy, receiving AEDs either monotherapy or polytherapy. Male predominance was 56%, and 60% were from rural areas and 40% were from urban areas. As per the modified Kuppuswamy scale, we analyzed socioeconomic class of these 100 patients and found that 40% belong to lower-middle-class family. Nearly 51% were diagnosed with generalized tonic clonic seizures, 30% were with febrile seizures, while focal, partial, absence, and myoclonic seizures, and hot water epilepsy were less in percentage. Almost 83% received monotherapy, while only 17% received polytherapy. Among monotherapy, 51.80% received older AEDs and 48.20% received newer drugs. Conclusion Although epilepsy can be controlled and managed effectively with older AEDs, an experience in management with newer AEDs is required to offer an additional advantage to patients to have better safety profile.

Photobiomodulation as a treatment for neurodegenerative disorders: current and future trends.

Photobiomodulation (PBM) is a rapidly growing as an innovative therapeutic modality for various types of diseases in recent years. Neuronal degeneration is irreversible process and it is proven to be difficult to slow down or stop the progression. Pharmacologic approaches to slow neuronal degeneration have been studied, but are limited due to concerns about the side effects. Therefore, it is necessary to develop a new therapeutic approach to stabilize neuronal degeneration and achieve neuronal protection against several neurodegenerative diseases. In this review, we have introduced several previous studies showing the positive effect of PBM over neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and different types of epilepsy. Despite excellent outcomes of animal researches, not many clinical studies are conducted or showed positive outcome of PBM against neurodegenerative disease. To achieve clinical application of PBM against neurodegenerative disorder, determination of exact mechanism and establishment of effective clinical protocol seems to be necessary.