Conventional Antiepileptic Drugs Research Articles

Unveiling the effects of nanoparticles-based antiepileptic drugs: Systematic review of in vivo studies

Background: Resistance and side effects of antiepileptic drugs (AEDs) pose a challenge in epilepsy therapy due to the limited drug bioavailability in penetrating the Blood-Brain Barrier (BBB). Nanoparticles can be one solution by encapsulating AEDs to enhance drug distribution to target cells. This study systematically assesses 1) the characteristics of nanoparticles, and 2) the potential of nanoparticle AEDs in managing seizures in experimental animal models. Methods: This systematic literature review is limited to studies published between 2013 and July 2023 in the PubMed, ScienceDirect, ProQuest, MEDLINE, and Scopus databases. Inclusion criteria encompass studies involving animal models of epilepsy, that exploring nanoparticle-based of AEDs. These studies compare the characteristics of nanoparticles and their antiepileptic efficacy with non-nanoparticle groups. Review articles, publications in non-English languages, and ongoing studies without published results are excluded. Result and Discussion: Fourteen studies met the inclusion criteria for this research. All studies utilized nanoparticles (n = 14). Lipid nanoparticles have a more compact size than any other nanoparticle, while the combination preparation method has an optimal nanoparticle formation in both lipid and polymeric nanoparticles. In animal model results indicated that nanoparticle-based drugs were beneficial in reducing seizure scores, improving seizure onset latency, and providing neuroprotective effects. Conclusion: The characteristics of nanoparticle drug delivery varied, influenced by formulation factors and preparation methods. Nanoparticle-based AEDs exhibit higher efficacy compared to conventional AEDs. All studies included present an opportunity for the development of epilepsy therapies, although future studies are needed to confirm these findings.

The effect of anticonvulsant drugs on serum lipid profile

BACKGROUND AND OBJECTIVES: Epilepsy is a potentially life-shortening brain disorder, the symptoms of which can be successfully treated in most patients with one or more antiepileptic drug (AED). The literature explains the association of AED therapy and dyslipidemia. The changes in lipid fraction may vary with different AED, age group, and study population. The present study was planned to assess the serum lipid profile of adult epileptic patients receiving phenytoin, carbamazepine or sodium valproate therapy and attending Neurology Outpatient Department of Government Medical College, Kottayam, compared to normal healthy controls. METHODOLOGY: A total of 150 epileptic patients on AED monotherapy attending the outpatient department of neurology were evaluated for serum lipid profile. Demographic data and medical history of consenting participants were collected by the use of a semi-structured questionnaire. Fifty age- and sex-matching healthy controls also underwent similar investigation. RESULTS AND DISCUSSION: Over 12 months, 150 patients were recruited with a mean age of 35.54 ± 10.72 years (male-to-female ratio 1:1.27). When compared to normal control population observed statistically significant high mean total cholesterol, triglyceride level in the group receiving phenytoin therapy for more than 1 year. Only significant hypertriglyceridemia is observed in carbamazepine and sodium valproate treated patients. A significant correlation between the duration of anticonvulsant therapy and lipid profile was established. CONCLUSION: Conventional anticonvulsants induce dyslipidemia and monitoring of lipid profile should be done routinely to decrease the morbidity and preserve the quality of life in these (asymptomatic) patients.

Comparative effectiveness-safety of conventional versus newer antiepileptics in epileptic patients in a tertiary care hospital, India

<b>Background</b>: As initial monotherapy, individuals with epilepsy are treated with both conventional and newer antiepileptic drugs (AEDs). The differences in their relative effectiveness and safety as a group, however, have not been thoroughly studied.<br /> <b>Objective:</b> To evaluate and compare the effectiveness and safety of conventional and newer anti-epileptic drugs in epileptic patients.<br /> <b>Material and methods:</b> A prospective comparative study was done in 126 epileptic patients. Patients divided into two groups Group A and B of 63 each received conventional and newer antiepileptic drugs respectively. Patients were allocated the AED based on type of epilepsy, patient characteristics and drug characteristics by the treating physician. Patients maintained a seizure diary which they filled weekly and this seizure diary was evaluated at 6 weeks and 12 weeks of follow up. Patients were assessed for adverse drug reactions (ADRs) at 0, 6 and 12 weeks of follow up and also for spontaneous reported ADRs at any time during the study.<br /> <b>Results:</b> In both group A and group B, our study demonstrated that seizure freedom, seizure severity, and time before first seizure did not differ significantly (p>0.5). Except for cognitive dysfunction, impaired memory, and swollen gums, which were more frequent in the conventional anti-epileptics group, the ADR profiles of both group of medications were similar. Phenytoin was found to cause gum swelling and cognitive impairment. No subject experienced a serious adverse event.<br /> <b>Conclusion:</b> Newer Antiepileptics as monotherapy are equally efficacious as conventional antiepileptics but may offer a better safety profile to epileptic patients.

Lippia origanoides essential oil possesses anticonvulsant effect in pentylenetetrazol-induced seizures in rats: a behavioral, electroencephalographic, and electromyographic study

Epilepsy is a neuronal disorder characterized by abnormal excitability of the brain, leading to seizures. Only around 66% of the epileptic patients respond adequately to treatment with existing conventional anticonvulsants, making it necessary to investigate new antiepileptic drugs. The growing research into natural products and their pharmacological properties has become increasingly promising, particularly in the study of essential oils, which are already widely used in popular culture for treating various diseases. The present study evaluated the anticonvulsant effects of Lippia origanoides essential oil (LOEO) (100 mg/kg i. p.) compared to diazepam (DZP) (5 mg/kg i. p.), and the combined administration of these two substances to control convulsions induced by pentylenetetrazol (PTZ) (60 mg/kg i. p.). This evaluation was carried out using 108 male Wistar rats, which were divided into two experiments. Experiment 1–Behavioral assessment: The animals were divided into 4 groups (n = 9): (I) saline solution + PTZ, (II) DZP + PTZ, (III) LOEO + PTZ, (IV) LOEO + DZP + PTZ. The convulsive behavior was induced 30 min after the administration of the tested anticonvulsant drugs, and the observation period lasted 30 min. Experiment 2- Electrocorticographic evaluation: The animals were divided into 8 groups (n = 9): (I) saline solution; (II) LOEO; (III) DZP; (IV) LOEO + DZP; (V) saline + PTZ, (VI) DZP + PTZ (VII) LOEO + PTZ, (VIII) LOEO + DZP + PTZ. PTZ was administered 30 min after LOEO and DZP treatments and electrocorticographic activity was assessed for 15 min. For the control groups, electromyographic recordings were performed in the 10th intercostal space to assess respiratory rate. The results demonstrated that Lippia origanoides essential oil increased the latency time for the appearance of isolated clonic seizures without loss of the postural reflex. The animals had a more intense decrease in respiratory rate when combined with LOEO + DZP. EEG recordings showed a reduction in firing amplitude in the LOEO-treated groups. The combining treatment with diazepam resulted in increased anticonvulsant effects. Therefore, treatment with Lippia origanoides essential oil was effective in controlling seizures, and its combination with diazepam may represent a future option for the treatment of difficult-to-control seizures.

Apolipoprotein E3 functionalized lipid-drug conjugated nanoparticles of Levetiracetam for enhanced delivery to the brain: In-vitro cell line studies and in-vivo study

A significant portion of brain-tumor patients suffer from ‘brain-tumor-related epilepsy (BTE)’ which results in depression, anxiety and hampered quality of life. Conventional anti-epileptic drugs indicate negative interaction with other drugs augmenting the poor outcome of overall therapy. Levetiracetam (LVM) has evidenced effectiveness for BTE but its hydrophilicity restricts the passage into blood-brain barrier. The majority of lipid nanoparticles fails to load hydrophilic drug sufficiently. Therefore, lipid-drug conjugates (LDC) were synthesized using stearic acid via amide bond formation confirmed by FTIR and NMR. The nanoparticles of synthesized LDC were prepared by solvent injection method followed by functionalization with Apolipoprotein E3 (ApoE3@LDC-NP). The nanoparticles were characterized by DSC, XRD, particle size (131.6 ± 1.24 nm), zeta potential (−15.6 ± 0.09 mV), and for storage stability. In-vitro release study indicated initial burst release of 20 ± 0.63 % followed by sustained release up to 30 h (66 ± 1.40 %) for ApoE3@LDC-NP. The cell-line study on HEK293 indicated no significant cytotoxic effect and greater cell uptake through U87MG cell line. The pharmacokinetic and bio-distribution study indicated 2.5-fold greater brain-targeting of ApoE3@LDC-NP as compared to LVM solution. It proved safe in the haemolysis study and exhibited the absence of tissue necrosis. Thus, ApoE3@LDC-NP might be a promising approach for effective brain-targeting of LVM for improved clinical response in BTE.

Investigating Neuroprotective Potential of Berberine, Levetiracetam and their Combination in the Management of Alzheimer's Disease Utilizing Drug Repurposing Strategy.

The aim of the present work was to evaluate the neuroprotective potential of berberine, levetiracetam and their combination in lead acetate-induced neurotoxicity by applying a drug repositioning approach. Alzheimer's disease (AD) is a neurodegenerative disease characterized by impairment of memory, disturbances in reasoning, planning, language and perception. Currently, there are only four drugs approved by US-FDA for AD; therefore, there is an extensive need for new drug development. The drug repositioning approach refers to the development of new uses for existing or abandoned pharmaceuticals. Several studies support the neuroprotective abilities of anti-oxidants resulting in neuronal protection against neurotoxins, suppression of oxidative stress and promotion of memory, learning and cognitive functions. Many natural polyphenols are being investigated as a potential therapeutic option for AD. Levetiracetam (LEV), a second-generation antiepileptic drug, is a new molecule that is clearly differentiated from conventional antiepileptic drugs by its pharmacologic properties. LEV also has been previously demonstrated to protect against oxidative stress-induced neurotoxicity in several models of seizures. Berberine (BBR) is an anti-inflammatory and anti-oxidant phytoconstituent. To study the therapeutic effect of berberine, levetiracetam and their physical mixture in lead acetate-induced neurotoxicity in Swiss albino mice for probable application in the management of Alzheimer's disease. Neurotoxicity was induced in Swiss albino mice by lead acetate. Behavioural parameters, such as transfer latency time and percentage alternation, were studied using Morris water maze (MWM), Elevated plus-maze test (EPM) and Y-maze for the assessment of improvement in learning and memory. Concentrations of acetylcholinesterase, MDA and GSH in the brain were also estimated. Brain samples were subjected to histopathological studies. Results revealed that the combination of BBR and LEV exhibited a significant neuroprotective effect by decreasing escape latency time and increasing time spent in the target quadrant in MWM. The combination also decreases transfer latency time in EPM and acetylcholinesterase levels in the brain as compared to standard donepezil. Reduced neuronal damage was also confirmed by the histopathological report. Leveteracitam, berberin and their combination resulted in the significant conservation of various behavioural, biochemical, enzymatic and anti-oxidant parameters that were evaluated. The neuroprotective effect of plain leveteracitam and berberin was significantly better than their combination. The anticipated synergism or additive effect was not observed with the combination of leveteracitam and berberin in lead acetate-induced neurotoxicity.

Eficacia de la Lamotrigina en pacientes epilépticos fármaco resistentes a tratamientos en un centro neurológico de referencia en la ciudad de Cali

Introducción: la epilepsia es una enfermedad neurológica frecuente, con una incidencia estimada de 50 por cada 100,000 habitantes y una prevalencia de cinco a diez por 1,000 habitantes en los países desarrollados. Se le llama refractaria cuando las crisis epilépticas son tan frecuentes que limitan la habilidad del paciente para vivir plenamente o cuando los efectos secundarios del manejo tratamiento son limitantes para el desarrollo normal de la persona pese al mejor manejo médico instaurado. La Lamotrigina es un antiepiléptico que inhibe los canales de sodio voltaje-dependientes, modulando la liberación presináptica de transmisores excitatorios de tipo glutamato y aspartato.
 Objetivo: determinar la efectividad de la Lamotrigina como monoterapia o en asociación con fármacos antiepilépticos convencionales en pacientes con Epilepsia Refractaria.
 Materiales y métodos: estudio descriptivo. Periodo de tiempo: mayo 2009 a noviembre 2012. Análisis de las variables por medio de frecuencias, promedios y proporciones.
 Resultados: muestra: 115 historias clínicas de pacientes con epilepsia refractaria. El 97,4% (112) tiene reducción en el número de crisis, siendo en el 85,2% (98) mayor o igual al 50%. Hubo un promedio de 9,45 crisis por mes, con una mediana de seis episodios, previo al manejo con este medicamento, mientras que tras la administración del medicamento, el promedio de episodios fue de 3,65 por mes, con mediana de 1 episodio/mes. El promedio de fármacos utilizados antes de introducir la Lamotrigina fue de 1,9 con un uso mínimo de 1 y máximo 6 y a partir del inicio de la Lamotrigina el promedio fue 2,3, con uso mínimo de 1 y máximo de 4 medicamentos.
 Conclusión: la Lamotrigina es un medicamento de última generación con adecuada efectividad y pocos efectos adversos que puede reducir de forma efectiva la frecuencia de crisis epilépticas en los pacientes de difícil manejo con refractariedad farmacológica.

Evaluation of Metabolic Parameters on Use of Newer Antiepileptics Versus Conventional Antiepileptics in Patients of Generalised Tonic-Clonic Seizure: An Observational Study.

Background and objective Epilepsy is the commonest serious neurological condition and around 50 million people live with epilepsy (PWE). Primary and secondary generalised tonic-clonic seizures (GTCS) together constitute up to 50% of adult and adolescent epilepsy. GTCS respond well to broad-spectrum AEDs like valproate, phenytoin, levetiracetam, lamotrigine, and topiramate. Carbamazepine and oxcarbazepine are considered alternatives. Metabolic derangements with the conventional AEDs (phenytoin causes loss of bone mass in women, phenytoin and carbamazepine produce increases in serum lipid and C-reactive protein, weight gain with valproate) are well documented. But, there is limited data regarding the effect of the newer AEDs on metabolic parameters. Thus, this study was undertaken to assess the effects of the newer AEDs on the metabolic profile of patients with epilepsy. Material and methods A prospective observational study was conducted in the Department of Pharmacology, in collaboration with the Department of Neurology at S.C.B. Medical College and Hospital, Cuttack. 100 diagnosed patients with GTCS receiving monotherapy of either conventional or newer anti-epileptics were included in the study. Their metabolic parameters like total cholesterol, serum sodium, serum TSH and fasting blood glucose were collected at baseline, three months, and six months. ADRs were collected during the entire study period and causality assessment was done using WHO-UMC Causality Assessment Scale. All the data were analysed using SPSS 20.0 after applying appropriate statistical tests. Results There was a significant increase in total cholesterol in all four groups (p=0.002) but a pathological increasein the phenytoin and oxcarbazepine groups. There was a significant rise in the serum TSH levels in all groups except levetiracetam, but a pathological increase was seen with phenytoin and valproate, i.e., the conventional ones. Statistically significant hyponatremia was seen with valproate and oxcarbazepine. A rise in the FBS was seen with both phenytoin and valproate (p=0.002) but a pathological rise was seen with phenytoin. Out of the total reported ADRs, 53.5% were seen with conventional AEDs, and the rest 46.5% were seen with newer ones. Conclusion The advent of newer anti-epileptic drugs has unfolded wider horizons to the treatment of epilepsy. Each of these drugs has a unique mechanism of action, making it less prone to resistance. Metabolic derangements are a key determinant in the compliance of these drugs as they can predispose to other co-morbidities. Periodic monitoring of the various metabolic parameters is useful and together with patient counselling can improve the effectiveness of the anti-epileptic drugs.

PRESCRIBING PATTERN OF ANTIEPILEPTIC DRUGS IN PEDIATRIC PATIENTS AT A TERTIARY CARE TEACHING HOSPITAL

Objectives: Epilepsy is one of the common neurological conditions worldwide. Methods: The observational, continuous, prospective, and single-center study was carried out to evaluate prescribing pattern of antiepileptic drugs (AEDs) in pediatric patients at a tertiary care teaching hospital of Gujarat for a total duration of 18 months. Patients were followed up monthly for the period of 3 months to evaluate seizure freedom, breakthrough seizure, and change in the AEDs, add-on therapy, treatment adherence and ADRs. Rationality was assessed for selection of drug and selection of the right dose according to recent guidelines. Results: Majority of patients in the age group of 7–9 years with mean age of 6.83 ± 3.09 years. Male-to-female ratio was 1.3:1. Total 73 AEDs were prescribed to pediatric epilepsy patients after diagnosis. Thirty-seven (69.80%) patients were prescribed AED on visit as monotherapy and 16 (30.20%) patients were prescribed polytherapy. Sodium valproate (77.36%) was most commonly prescribed AED followed by levetiracetam and carbamazepine. Most of AEDs were prescribed according to NICE guideline and by generic name. Conclusion: Conventional AEDs are still used as first line of treatment for pediatric epilepsy patients, although newer AEDs also frequently prescribed as add on or primary drug. Low birth weight, NICU admission, and non-compliance to treatment are associated with breakthrough seizures.

Possible immuno-modulatory effects of tocilizumab in patients with refractory status epilepticus.

Refractory Status Epilepticus (RSE) is a neurologic emergency that carries a high risk of mortality and morbidity. Every year, there are about 200,000 cases in the United States, affecting people of all ages. This study aimed to investigate the possible immuno-modulatory effect of tocilizumab in RSE patients receiving conventional anti-epileptic drugs. 50 outpatients who fulfilled the inclusion requirements for RSE were recruited in this randomized, controlled, and prospective study. The patients were divided into two groups randomly (n=25); the control group received standard RSE treatment, consisting of propofol, pentobarbital, and midazolam, and the tocilizumab group received standard RSE treatment plus tocilizumab. A neurologist evaluated each patient at the beginning of the therapy and after 3 months. Before and after treatment, serum nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and serum electrolytes were assessed. The tocilizumab group showed a statistically significant reduction in the level of assessed parameters in comparison with the control group. Tocilizumab might be a novel adjuvant anti-inflammatory medication in managing RSE.

Neuroprotective effect and herbal-drug pharmacokinetic interaction of Gastrodia elata extract on valproic acid

Valproic acid (VPA) is a widely used antiepileptic drug, and the herbal extract of Gastrodia elata exerts an anticonvulsant effect. However, few studies have investigated the pharmacokinetic and pharmacodynamic interactions between G. elata extract and VPA. We hypothesize that G. elata extract increases the VPA levels in the brain and enhances the antiepileptic effects of VPA, and this synergistic effect is mediated by transporters at the bloodbrain barrier (BBB). We performed microdialysis on pilocarpine-induced epileptic model rats in vivo to investigate this hypothesis. The results demonstrated that cotreatment with G. elata extract and VPA ameliorated drug-resistant epilepsy by increasing the VPA levels in the brain. In addition, G. elata extract and VPA exerted synergistic anticonvulsive effects to decrease the seizure severity by protecting neurons in the hippocampus and altering the DOPAC and 5-HT levels. However, these phenomena were partially blocked by the organic anion transporter peptide (OATP) inhibitor cyclosporine A (CsA; 20 mg/kg, i.p.), which demonstrated that the increase in the VPA level in the brain was modulated by the transporter OATP. This study provides a comprehensive strategy for assessing the interaction between traditional medicines and conventional antiepileptic drugs in a status epilepticus animal model.

Cannabis-based magistral formulation is highly effective as an adjuvant treatment in drug-resistant focal epilepsy in adult patients: an open-label prospective cohort study.

The safety and efficacy of a formulation high in cannabidiol (CBD) and low in ∆9-tetrahydrocannabinol (THC) to treat drug-resistant epilepsy have been examined previously in children, but not in adult population. The aim of this study was to evaluate whether CBD-rich oil, as an add-on treatment to conventional antiepileptic drugs, was effective, safe, and well-tolerated in adults with drug-resistant focal epilepsy (DRFE). An open-label, prospective cohort, single-center in adult patients with DRFE, were receiving stable doses of antiepileptic drugs (AEDs). A cannabis based-magistral formulation (CBMF) (100 mg/ml CBD and THC <1.9 mg/ml) was administrated 0.1 ml sublingually every 12 hours, up-titrated weekly. The primary outcome was to establish a reduction in seizures frequency >50% at 12 weeks. Adverse-drug reactions monitoring was done. p-value <0.05 was statistically significant. Between August 2020 and July 2022, 44 (38.6%) patients completed >3 months of follow-up. The median daily dose of CBD was 200 mg, that of THC was 4 mg, and that of CBD per kilogram of weight was 3.7 mg. The median number of seizures per month before CBD treatment was 11, and after CBD treatment was 2.5 (p<0.001). A reduction in seizures >50% at 12 week was achieved in 79.5% of the patients. The median percentage change in seizure frequency per month was 84.1% at 12 weeks. Five patients reported any adverse-drug reactions. The CBMF is a highly effective and safety therapy to treat adult patients with DRFE. The reduction in seizures frequency is maintained over time.

Regulation of Inflammation-Related Genes through Fosl1 Suppression in a Levetiracetam-Treated Pilocarpine-Induced Status Epilepticus Mouse Model

Levetiracetam (LEV) suppresses the upregulation of proinflammatory molecules that occurs during epileptogenesis after status epilepticus (SE). Based on previous studies, LEV likely helps prevent the onset of epilepsy after insults to the brain, unlike other conventional anti-epileptic drugs. Recently, we discovered that the increase in Fosl1 expression that occurs after lipopolysaccharide (LPS) stimulation is suppressed by LEV and that Fosl1 inhibition suppresses inflammation in BV-2 microglial cells. These data indicate that Fosl1 is an important target of LEV and a key factor in preventing epilepsy onset. In this study, we examined the effects of LEV on Fosl1 expression and neuroinflammation in vivo. During epileptogenesis, the post-SE upregulation of hippocampal levels of Fosl1 and many inflammatory factors were suppressed by LEV. Fosl1 expression showed a characteristic pattern different from that of the expression of Fos, an immediate-early gene belonging to the same Fos family. At 2 days after SE, Fosl1 was predominantly expressed in astrocytes but was rarely detected in microglia, whereas Fos expression was distributed in various brain cell types. The expression of A2 astrocyte markers was similar to that of Fosl1 and was significantly suppressed by LEV. These results suggest that LEV may regulate astrocyte reactivity through regulation of Fosl1.

TO COMPARE EFFICACY, TOLERABILITY AND QUALITY OF LIFE WITH CONVENTIONAL AND NEWER ANTIEPILEPTIC AS MONOTHERAPY IN NEWLY DIAGNOSED PATIENTS OF EPILEPSY.

Background: Quality of life plays an important role in patients of epilepsy and is the most neglected part during management. The antiepileptic drugs treatment results in seizure control but adversely affect the quality of life in patients on drugs taken for the treatment of epilepsy An observational analytical study was conducted in the Department of pharmacology withMethods: Department of Neurology of Himalayan Institute of Medical Sciences, Dehradun over one year. Total of 120 patients fullling the inclusion criteria with diagnosis of epilepsy were enrolled and divided into two groups based on physicians discretion . Group A were on the conventional antiepileptic drugs , group B received the newer antiepileptic drugs and followed up for 12 weeks. Patients were evaluated for quality of life by QOLIE-10 questionnaire at baseline and 12 weeks, assessed for seizure control and drug related adverse effects. There was signicantResults: improvement in quality of life, in both the groups as compared to baseline (p&lt;0.05) at 12 weeks but there was not signicant change in quality of life in conventional and newer groups. The patients who reported total seizure freedom at 6 weeks was 93% and 90% for older and newer groups respectively .Both groups achieved complete seizure control at 12 weeks. Adverse events reported in patients on conventional groups were more as compared to newer group. Quality of life improved in both group of patients on newer and conventional antiepileptic drugs, withConclusions: similar seizure control but decreased number of adverse effect of newer than on conventional antiepileptic drugs .

Demographic Profile and Prescribing Patterns of Anti-epileptic Drugs in Indian Epilepsy Patients: Electronic Medical Record-Based Nation-Wide Retrospective Cohort Study.

The aim of this study was to provide real-world data on clinical characteristics, risk factors, and treatment patterns in Indian patients with epilepsy. Electronic medical record (EMR) data of patients diagnosed with epilepsy between January 2001 and December 2019, which included demographics, diagnosis, anti-epileptic drug usage, and underlying risk factors were evaluated. The majority of patients were between the age group of 18 and 55 years (n=3,186), with males accounting for 62% and the remaining 38% being females. Further, the most common comorbidity was hypertension (23.3%, n=1,470), followed by diabetes mellitus (10.8%, n=683) and depression (9.4%, n=597). The most prevalent form of epilepsy was focal epilepsy (n=5,141 81.4%), followed by generalized epilepsy (n=601). Focal epilepsy was most prevalent in males (62%, n=3,167) and most common in the age group of 18-55 years (50.3%, n=2588). Anti-epileptic drug (AED) usage data from 6,318 patients showed that the most commonly prescribed AED alone or in combination for both focal and generalized epilepsy was levetiracetam (41.8%, n= 2645). Data collected from this study are aligned but do not completely agree with the Guidelines for the Management of Epilepsy in India (GEMIND). This affirms treatment initiation with AED monotherapy; however, the treatment choices do not necessarily follow the recommended guidelines to select conventional AEDs, at low strengths, at initiation.

Evaluation of the anticonvulsant effect of carvacrol in Pentylenetetrazole (PTZ)-induced seizures in male mice: N-Methyl-D-Aspartic Acid receptor role

Background. Epilepsy is one of the most common neurological disorders after stroke. Due to the side effects and poor response of conventional anticonvulsant drugs, researchers have turned their attention to find new drugs. Carvacrol is a phenolic compound with neuroprotective, anti-inflammatory, antioxidant and anticonvulsant effects. The aim of the study was to investigate the anticonvulsant effects of carvacrol in PTZ-induced seizures in male mice and to investigate the role of N-Methyl-D-Aspartic Acid (NMDA) receptor. Methods. In the present experimental study, 90 mice were randomly divided into 9 groups (n=10). Drugs were injected intraperitoneally 30 minutes before PTZ injection. Then, seizure onset time, serum and brain antioxidant capacity (TAC) and malondialdehyde (MDA) and NMDA receptor gene expression in the hippocampus were examined. Results. Seizure onset time in the group received carvacrol (20 and 40 mg/kg) was significantly longer than the PTZ group (P&lt;0.05). Treatment with carvacrol (20 and 40 mg/kg) significantly increased serum and brain antioxidant capacity and reduced serum and brain MDA in compared to the PTZ group (at doses of 5, 10, 20 and 40 mg/kg). The expression of NR2A and NR2B subunits of hippocampal NMDA receptors in carvacrol-received mice was significantly lower than the PTZ group (P&lt;0.05). Conclusion. Carvacrol has anticonvulsant effects, possibly by inhibiting oxidative stress and reducing the expression of subunits of NMDA receptors.

Endocannabinoid-Mediated Control of Neural Circuit Excitability and Epileptic Seizures.

Research on endocannabinoid signaling has greatly advanced our understanding of how the excitability of neural circuits is controlled in health and disease. In general, endocannabinoid signaling at excitatory synapses suppresses excitability by inhibiting glutamate release, while that at inhibitory synapses promotes excitability by inhibiting GABA release, although there are some exceptions in genetically epileptic animal models. In the epileptic brain, the physiological distributions of endocannabinoid signaling molecules are disrupted during epileptogenesis, contributing to the occurrence of spontaneous seizures. However, it is still unknown how endocannabinoid signaling changes during seizures and how the redistribution of endocannabinoid signaling molecules proceeds during epileptogenesis. Recent development of cannabinoid sensors has enabled us to investigate endocannabinoid signaling in much greater spatial and temporal details than before. Application of cannabinoid sensors to epilepsy research has elucidated activity-dependent changes in endocannabinoid signaling during seizures. Furthermore, recent endocannabinoid research has paved the way for the clinical use of cannabidiol for the treatment of refractory epilepsy, such as Dravet syndrome, Lennox-Gastaut syndrome and tuberous sclerosis complex. Cannabidiol significantly reduces seizures and is considered to have comparable tolerability to conventional antiepileptic drugs. In this article, we introduce recent advances in research on the roles of endocannabinoid signaling in epileptic seizures and discuss future directions.

Efficacy and prognosis of long-term, high-dose steroid therapy for Lennox–Gastaut syndrome

ObjectiveLennox–Gastaut syndrome (LGS) is a severe form of developmental and epileptic encephalopathy that is highly resistant to treatment with conventional anti-epileptic drugs and non-pharmacological therapies. In the present study, we aimed to investigate the efficacy of long-term, high-dose steroid therapy and its effect on prognosis in children with LGS. MethodsThis prospective study included patients with LGS who received long-term, high-dose steroid therapy beginning in November 2016. Prednisolone (60 mg per day) was administered for 2 weeks, following which the dosage was reduced to 60 mg on alternate days for 12 weeks. The drug was then slowly tapered over the next 3 months. The primary outcome was a reduction in seizure frequency relative to baseline at 14 weeks. The secondary outcome was whether patients had become seizure-free at 1 year. ResultsAmong 44 patients, 30 (68.2%) experienced a reduction in seizure frequency of more than 50%, including 26 (59.1%) with complete seizure control who were classified as the responder group. The remaining 14 (31.8%) were classified as the non-responder group after 14 weeks of treatment. Twenty patients (45.5%, 20/44) remained seizure-free after 1 year of treatment. However, 10 patients (33.3%, 10/30) in the responder group relapsed within a year. Improvements in electroencephalography (EEG) findings tended to be consistent with seizure outcomes. All patients had side effects of weight gain and Cushing’s face, but most adverse effects were mild and transient. ConclusionLong-term, high-dose steroid therapy can be considered an effective treatment option for children with intractable LGS.

The Protective Role of E-64d in Hippocampal Excitotoxic Neuronal Injury Induced by Glutamate in HT22 Hippocampal Neuronal Cells.

Epilepsy is the most common childhood neurologic disorder. Status epilepticus (SE), which refers to continuous epileptic seizures, occurs more frequently in children than in adults, and approximately 40–50% of all cases occur in children under 2 years of age. Conventional antiepileptic drugs currently used in clinical practice have a number of adverse side effects. Drug-resistant epilepsy (DRE) can progressively develop in children with persistent SE, necessitating the development of novel therapeutic drugs. During SE, the persistent activation of neurons leads to decreased glutamate clearance with corresponding glutamate accumulation in the synaptic extracellular space, increasing the chance of neuronal excitotoxicity. Our previous study demonstrated that after developmental seizures in rats, E-64d exerts a neuroprotective effect on the seizure-induced brain damage by modulating lipid metabolism enzymes, especially ApoE and ApoJ/clusterin. In this study, we investigated the impact and mechanisms of E-64d administration on neuronal excitotoxicity. To test our hypothesis that E-64d confers neuroprotective effects by regulating autophagy and mitochondrial pathway activity, we simulated neuronal excitotoxicity in vitro using an immortalized hippocampal neuron cell line (HT22). We found that E-64d improved cell viability while reducing oxidative stress and neuronal apoptosis. In addition, E-64d treatment regulated mitochondrial pathway activity and inhibited chaperone-mediated autophagy in HT22 cells. Our findings indicate that E-64d may alleviate glutamate-induced damage via regulation of mitochondrial fission and apoptosis, as well as inhibition of chaperone-mediated autophagy. Thus, E-64d may be a promising therapeutic treatment for hippocampal injury associated with SE.

Anticonvulsant Activity of Helianthus tuberosus Against Maximal Electroshock Induced Convulsions in Rats

Epilepsy is an episodic brain dysfunction featured by recurring erratic spontaneous seizures followed by cognitive, social, neurobiological, and psychological consequences. Conventional anti-epileptic drugs are associated with several untoward effects, and hence long-term treatment compliance is a major problem in the management of epilepsy. Herbal drugs have shown promising efficacy as potent anticonvulsants in the past few years. In light of this, the anticonvulsant effect of alcoholic extract of leaves of Helianthus tuberosus (AHT) against maximal electroshock (MES) induced convulsions was investigated. In the present investigation, an indigenous plant, H. tuberosus was studied for its protective effect against maximal electroshock (MES) induced convulsions in Wistar albino rats. The rats were pre-treated with different doses (100, 200, 400 mg/kg) of alcoholic extract of leaves of H. tuberosus for 14 days, and then, they were subjected to maximal electroshock seizures (40 mA for 0.2 seconds) treatment. Alcoholic extract of leaves of H. tuberosus at the dose of 400 mg/kg significantly reduced the duration of hind limb extension and the protection of rats against maximal electroshock-induced seizures. The reference standards phenytoin (20 mg/kg) provided complete protection. Thus, the present study revealed an anticonvulsant effect of H. tuberosus against maximal electroshock-induced convulsions in rats.