Common Antiepileptic Drugs Research Articles

Ferroptosis promotes valproate-induced liver steatosis in vitro and in vivo

Valproic acid (VPA), a common antiepileptic drug, can cause liver steatosis after long-term therapy. However, an impact of ferroptosis on VPA-induced liver steatosis has not been investigated. In the study, treatment with VPA promoted ferroptosis in the livers of mice by elevating ferrous iron (Fe2+) levels derived from the increased absorption by transferrin receptor 1 (TFR1) and the decreased storage by ferritin (FTH1 and FTL), disrupting the redox balance via reduced levels of solute carrier family 7 member 11 (SLC7A11), glutathione (GSH), and glutathione peroxidase 4 (GPX4), and augmenting acyl-CoA synthetase long-chain family member 4 (ACSL4) -mediated lipid peroxide generation, accompanied by enhanced liver steatosis. All the changes were significantly reversed by co-treatment with an iron-chelating agent, deferoxamine mesylate (DFO) and a ferroptosis inhibitor, ferrostatin-1 (Fer-1). Similarly, the increases in Fe2+, TFR1, and ACSL4 levels, as well as the decreases in GSH, GPX4, and ferroportin (FPN) levels, were detected in VPA-treated HepG2 cells. These changes were also attenuated after co-treatment with Fer-1. It demonstrates that ferroptosis promotes VPA-induced liver steatosis through iron overload, inhibition of the GSH-GPX4 axis, and upregulation of ACSL4. It offers a potential therapy targeting ferroptosis for patients with liver steatosis following VPA treatment.

Thyroid Hormone Status in Children Taking Antiepileptic Drugs (AEDs): An Experience in a Tertiary Care Hospital of Bangladesh.

Introduction: Antiepileptic drugs (AEDs) may alter thyroid hormone homeostasis at the level of biosynthesis, release, transport, metabolism and excretion of thyroid hormones. The purpose of the study was to see the thyroid hormone status in children with epilepsy treating with common antiepileptic drugs. Materials & Method: The cross-sectional study was carried out in department of pediatric neurology, National Institute of Neurosciences and Hospital (NINS), Dhaka. One hundred and sixty epileptic children aged 1 year to 14 years who were on monotherapy or polytherapy with the most commonly used Antiepileptic drugs (AEDs) for at least 6 months or more were enrolled. Serum TSH and FT4 were measured in all selected patients with early morning serum sample. Result: Nearly one third of study subjects had thyroid dysfunction, most of which were Subclinical hypothyroidism (SCH). The frequency of SCH was 29.2% in carbamazepine(CBZ), 50% in oxcabazepine (OXC), 28.6% in phenobarbitone(PHB) and 13% in valproic acid (VPA) treated epileptic children. No child was found to have subclinical hypothyroidism with topiramate and ethosuximide monotherapy. Antiepileptic drugs (AEDs) monotherapy or polytherapy had no significant difference in alteration on thyroid hormone level. Use of CBZ for long duration significantly altered thyroid function. Doses of Antiepileptic drugs (AEDs) didn’t show any significant thyroid dysfunction. Conclusion: Commonly used Antiepileptic drugs (AEDs) in children with epilepsy were associated with alteration of thyroid hormones, most commonly subclinical hypothyroidism. BANGLADESH J CHILD HEALTH 2022; VOL 46 (2) : 58-64

Valproic Acid Causes Redox-Regulated Post-Translational Protein Modifications That Are Dependent upon P19 Cellular Differentiation States.

Valproic acid (VPA) is a common anti-epileptic drug and known neurodevelopmental toxicant. Although the exact mechanism of VPA toxicity remains unknown, recent findings show that VPA disrupts redox signaling in undifferentiated cells but has little effect on fully differentiated neurons. Redox imbalances often alter oxidative post-translational protein modifications and could affect embryogenesis if developmentally critical proteins are targeted. We hypothesize that VPA causes redox-sensitive post-translational protein modifications that are dependent upon cellular differentiation states. Undifferentiated P19 cells and P19-derived neurons were treated with VPA alone or pretreated with D3T, an inducer of the nuclear factor erythroid 2-related factor 2 (NRF2) antioxidant pathway, prior to VPA exposure. Undifferentiated cells treated with VPA alone exhibited an oxidized glutathione redox couple and increased overall protein oxidation, whereas differentiated neurons were protected from protein oxidation via increased S-glutathionylation. Pretreatment with D3T prevented the effects of VPA exposure in undifferentiated cells. Taken together, our findings support redox-sensitive post-translational protein alterations in undifferentiated cells as a mechanism of VPA-induced developmental toxicity and propose NRF2 activation as a means to preserve proper neurogenesis.

Simultaneous monitoring of seven antiepileptic drugs by dried blood spot and dried plasma spot sampling: method validation and clinical application of a LC–MS/MS-based technique

Alternative blood sampling strategy can enhance the application of therapeutic drug monitoring (TDM), then improve precision therapy and medication compliance. In developing nations, alternative sampling strategy that allows self-sampling and room temperature transport is especially important. This study validates the use of dried blood spot (DBS) and dried plasma spot (DPS) sampling along with liquid chromatography–tandem mass spectrometry (LC–MS/MS) for analyzing seven common antiepileptic drugs (AEDs) (phenytoin, lamotrigine, levetiracetam, topiramate, carbamazepine, oxcarbazepine and its active metabolite 10,11-dihydro-10-hydroxy carbamazepine) and evaluates their applicability to clinical practice. Following simple protein precipitation with acetonitrile, the AEDs were separated on a C18 column by gradient elution with a mobile phase consisting of acetonitrile–water–0.1% formic acid at a flow rate of 0.65 mL/min. The method provided linear analysis over the tested concentration ranges, with a total run time of 7 min. Intra- and inter-assay precision for all quality controls were ≤12% with accuracies of 85.9%–113%. The average extraction efficiencies were 69.0%–92.4% for DBS and 65.9%–96.5% for DPS, and no significant matrix effects were observed. The AEDs were stable in all samples for seven days at room temprature and 40°C. There was good correlation between the dry and wet plasma concentrations with greater accuracy for DPS compared to DBS indicating that alternative sampling strategy using DBS and DPS are suitable for monitoring the concentrations of AEDs with satisfied performance and logistical advantages.

Fast degradation of carbamazepine in water by electric discharge plasma

The proliferation of pharmaceuticals in the aqueous environment has adversely impact on human health and ecosystem balance. Pharmaceutical contaminations are difficult to remove effectively by conventional treatment technologies. In order to degrade carbamazepine (CBZ) efficiently, a common antiepileptic drug, three plasma discharge modes were studied, including liquid-phase discharge, air gas-liquid jet and dielectric barrier discharge. It is noteworthy that the degradation efficiency and energy yield reached to highest levels (0.11 g/kWh) when operating at 225 W input power under liquid phase discharge, compared with the other discharge modes. The parameters of concentration, electrode distance, volume, input power and frequency of the discharge were also evaluated and optimized. Plasma emission spectroscopy revealed the degradation process is mainly attributed to reactive oxygen species (ROS), while the role of reactive nitrogen species was not significant. The contributions of diverse ROS were assessed by radical quenching experiments, including p-benzoquinone, p-phthalic acid and tert-butanol. The possible degradation intermediates and pathways of CBZ were tested and analyzed by liquid chromatography-mass spectrometry (LC-MS). Comprehensively consideration of cleanliness, degradation efficiency and application difficulty, liquid-phase discharge treatment is a promising technology for water treatment.

Arachidonic acid modulates the cellular energetics of human pluripotent stem cells and protects the embryoid bodies from embryotoxicity effects in vitro

Arachidonic acid (AA), an ω-6 polyunsaturated fatty acid involved in signalling pathways that drive cell fate decisions, has an enhancing role in the immunomodulatory effect on mesenchymal stem cells and the vasculogenesis of embryonic stem cells. 3D embryoid bodies (EBs) from pluripotent stem cells (PSCs) have been used as in vitro models for embryotoxicity for various compounds/drugs. Valproic acid (VA), a common anti-epileptic drug, is known to be embryotoxic and cause malformations in embryos. As early embryogenesis depends on AA, we investigated the embryo protective effects of AA against the embryotoxic drug VA in this study. The effects of AA on the proliferation and cell cycle parameters of PSCs were studied. In particular, the potential of AA to abrogate VA-induced embryotoxicity in vitro was evaluated using ROS detection and antioxidant assays. In response to AA, we observed modulation in cell proliferation of induced pluripotent stem cells (iPSCs) and pluripotent NTERA-2 embryonal carcinoma (EC) cells. The present study substantiates the cytoprotective effects of AA against VA. These results imply that AA plays a critical role in the proliferation and differentiation of iPSCs and EC cells and protects the EBs from cytotoxic damage, thereby ensuring normal embryogenesis. Thus, the bioactive lipid AA may be explored for supplementation to benefit pregnant women treated with long-term anti-epileptic drugs to prevent in-utero fetal growth malformations.

Association Between Antiepileptic Drugs and Incident Parkinson Disease

Recent studies have highlighted an association between epilepsy and Parkinson disease (PD). The role of antiepileptic drugs (AEDs) has not been explored. To investigate the association between AEDs and incident PD. This nested case-control study started collecting data from the UK Biobank (UKB) in 2006, and data were extracted on June 30, 2021. Individuals with linked primary care prescription data were included. Cases were defined as individuals with a Hospital Episode Statistics (HES)-coded diagnosis of PD. Controls were matched 6:1 for age, sex, race and ethnicity, and socioeconomic status. Prescription records were searched for AEDs prescribed prior to diagnosis of PD. The UKB is a longitudinal cohort study with more than 500 000 participants; 45% of individuals in the UKB have linked primary care prescription data. Participants living in the UK aged between 40 and 69 years were recruited to the UKB between 2006 and 2010. All participants with UKB-linked primary care prescription data (n = 222 106) were eligible for enrollment in the study. Individuals with only a self-reported PD diagnosis or missing data for the matching variables were excluded. In total, 1477 individuals were excluded; 49 were excluded due to having only self-reported PD, and 1428 were excluded due to missing data. Exposure to AEDs (carbamazepine, lamotrigine, levetiracetam, and sodium valproate) was defined using routinely collected prescription data derived from primary care. Odds ratios and 95% CIs were calculated using adjusted logistic regression models for individuals prescribed AEDs before the first date of HES-coded diagnosis of PD. In this case-control study, there were 1433 individuals with an HES-coded PD diagnosis (cases) and 8598 controls in the analysis. Of the 1433 individuals, 873 (60.9%) were male, 1397 (97.5%) had their race and ethnicity recorded as White, and their median age was 71 years (IQR, 65-75 years). An association was found between AED prescriptions and incident PD (odds ratio, 1.80; 95% CI, 1.35-2.40). There was a trend for a greater number of prescription issues and multiple AEDs being associated with a greater risk of PD. This study, the first to systematically look at PD risk in individuals prescribed the most common AEDs, to our knowledge, found evidence of an association between AEDs and incident PD. With the recent literature demonstrating an association between epilepsy and PD, this study provides further insights.

Sensitive determination of ethosuximide in human fluids by electromembrane extraction coupled with high performance liquid chromatography ultraviolet spectroscopy

AbstractEthosuximide (ETX) is a common antiepileptic drug in the first line of absence epilepsy. In this study, for the first time, an economical and efficient electro‐membrane (EME) method for determination of ETX in a complex biological matrix using HPLC‐UV has been developed. Factors affecting conventional EME were evaluated. 1‐Octanol was immobilized in a polypropylene membrane and a voltage of 35 V was applied between two platinum electrodes for 15 min. The pH of acceptor and donor phases for ionization of ETX was adjusted to 13 and 11, respectively. Under optimal microextraction conditions, the enrichment factor was 21.02 and the linear range of ETX was 0.25 to 8.00 μg/mL with an acceptable R2 ≥ 0.9986. Inter‐day and intra‐day precision and accuracy of the suggested method were calculated with RSD < 9.5% and relative error <7.0%, respectively. The mean relative recovery of ETX in the human saliva and plasma samples was 81.68% and 74.47, respectively; while limit of detection and quantification concentrations were 0.08 and 0.25 μg/mL, respectively. Furthermore, to evaluate the application of the method, plasma and saliva samples of volunteers administering a single dose of ETX were analyzed successfully by EME‐HPLC‐UV method.

Degradation of carbamazepine from wastewater by ultrasound-enhanced zero-valent iron -activated persulfate system (US/Fe0/PS): kinetics, intermediates and pathways

ABSTRACT Carbamazepine (CBZ) is a common antiepileptic drug. CBZ enters the environment through unreasonable and standardized ways such as human and animal metabolites, discarded drugs, and more than half of its metabolites are released into the environment. Since CBZ is not easy to be degraded, continuous input of CBZ into the water environment will cause long-term impact on the water ecological environment and seriously endanger human health. Aiming at how to degrade wastewater containing carbamazepine, studies were conducted on the degradation of carbamazepine by ultrasound/zero-valent iron/persulfate system (US/ F e 0 /PS). Firstly, the removal effects of carbamazepine by different systems, such as ultrasound/sodium persulfate (US/PS), zero-valent iron/persulfate system ( F e 0 /PS) and US/ F e 0 /PS, were compared; Secondly, the influence of factors, such as ultrasonic power, sodium persulfate dosage, zero-valent iron dosage, reaction temperature, pH, etc., on the reaction was investigated by the control variables method. Results show that ultrasound power, PS concentration, pH and temperature have a great influence on the removal of carbamazepine in US/Fe0/PS reaction system. Besides, the optimum parameters for degradation of carbamazepine with US/ F e 0 /PS reaction system were determined ([CBZ]0 = 0.025 mM; [PS]0 = 0.4 mM; Fe0 = 4.0 mg/L; ultrasonic power = 40 W; T = 30 ℃; initial pH = 5.0). Finally, the intermediates and degradation pathways of carbamazepine by US/ F e 0 /PS system were analyzed and speculated. It was inferred that two intermediates were generated during the degradation of carbamazepine, mainly through the ring opening and decyclization of piperazine rings. It was proved that process US/ F e 0 /PS has a very important application value in the degradation of antibiotic-containing wastewater.

Anti‑tumor effects of anti‑epileptic drugs in malignant glioma cells.

Patients with glioblastoma frequently suffer epileptic seizures and often require anticonvulsant therapy during the treatment course. The present study investigated four common antiepileptic drugs, perampanel, carbamazepine (CBZ), sodium valproate (VPA) and levetiracetam (LEV), which are expected to have antitumor effects, and determined the most beneficial drug for the treatment of malignant glioma by comparing antitumor effects such as inhibition of cell proliferation and suppression of migration and invasion (using Transwell assays). The inhibition of cell growth was investigated using six malignant glioma cell lines (A‑172, AM‑38, T98G, U‑138MG, U‑251MG and YH‑13). Significant inhibition of cell proliferation was observed in all six cell lines treated with perampanel, three cell lines treated with CBZ, four cell lines treated with VPA and two cell lines treated with LEV at the therapeutic blood concentration levels for the drugs to be used as antiepileptics. Further antitumor effects in combination with temozolomide were investigated using T98G and U‑251MG cell lines, and were confirmed in both cell lines with perampanel and in T98G cells with LEV, but not observed with CBZ and VPA. Cell migration was significantly suppressed in both T98G and U‑251MG cell lines with perampanel, but not with CBZ, VPA or LEV. To investigate the mechanisms by which perampanel suppresses the migration of malignant glioma cells, the expression of mRNA related to epithelial‑mesenchymal transition following perampanel treatment was analyzed using reverse transcription‑quantitative PCR in the T98G and U‑251MG cell lines. The expression of Rac1 and RhoA, which constitute the cytoskeleton that enhances cell motility, were reduced in both cell lines. Furthermore, the expression of the mesenchymal marker N‑cadherin, which promotes cell migration and infiltration, was decreased, but the expression of the epithelial marker E‑cadherin, which strengthens cell‑cell adhesion and reduces cell motility, was increased. Furthermore, the expression of matrix metalloproteinase‑2, a proteolytic enzyme, was reduced. These effects may reduce cell motility and increase adhesion between cells, suggesting that perampanel treatment suppressed cell migration. In conclusion, the present study suggests that perampanel may be more beneficial in terms of antitumor efficacy than other antiepileptic drugs for the treatment of malignant glioma.

Valproic Acid Overdose: Case Report and Literature Review

BackgroundValproic acid (VPA) is a common antiepileptic drug that is also used routinely for various psychiatric disorders. VPA toxicity typically manifests as central nervous system depression, while hyperammonemic encephalopathy and hepatotoxicity are potentially life-threatening complications. Case ReportWe describe the case of a 56-year-old man who presented to the emergency department after an intentional VPA overdose, was found to have hyperammonemia, and was treated with L-carnitine exclusively. He was subsequently admitted to the hospital for monitoring and serial laboratory testing. Why Should an Emergency Physician Be Aware of This?Although VPA toxicity has conventionally been managed by gastric decontamination, L-carnitine, and, in severe and refractory cases, extracorporeal removal, recent literature supports the use of carbapenem antibiotics, particularly meropenem. Thus, we report the details of current treatment modalities for VPA toxicity by reviewing current literature.

Effects of naringin and valproate interaction on liver steatosis and dyslipidaemia parameters in male C57BL6 mice.

Valproate is a common antiepileptic drug whose adverse effects include liver steatosis and dyslipidaemia. The aim of our study was to see how natural flavonoid antioxidant naringin would interact with valproate and attenuate these adverse effects. For this reason we treated male C57BL6 mice with a combination of 150 mg/kg of valproate and 25 mg/kg naringin every day for 10 days and compared their serum triglycerides, cholesterol, LDL, HDL, VLDL, and liver PPAR-alpha, PGC-1 alpha, ACOX1, Nrf2, SOD, CAT, GSH, and histological signs of steatosis. Valproate increased lipid peroxidation parameters and caused pronounced microvesicular steatosis throughout the hepatic lobule in all acinar zones, but naringin co-administration limited steatosis to the lobule periphery. In addition, it nearly restored total serum cholesterol, LDL, and triglycerides and liver ACOX1 and MDA to control levels. and upregulated PPAR-alpha and PGC-1 alpha, otherwise severely downregulated by valproate. It also increased SOD activity. All these findings suggest that naringin modulates key lipid metabolism regulators and should further be investigated in this model, either alone or combined with other lipid regulating drugs or molecules.

Pyridoxine-dependent epilepsy (PDE-ALDH7A1) in adulthood: A Dutch pilot study exploring clinical and patient-reported outcomes

BackgroundLittle is known about pyridoxine-dependent epilepsy due to α-aminoadipic semialdehyde dehydrogenase deficiency (PDE-ALDH7A1) in adulthood, as the genetic basis of the disorder has only been elucidated 15 years ago. This creates a knowledge gap for physicians, pediatric patients and their parents, which was aimed to address in this study using clinical data as well as patient-reported outcome measures (PROMs) for the patient's perspective. MethodsDutch, genetically confirmed PDE-ALDH7A1 patients ≥18 years were eligible for inclusion. Clinical data were collected as well as PROMs (PROMIS item banks Anxiety, Depression, Anger, Physical Functioning, Cognitive Functioning, Cognitive Abilities, Ability to Participate and Satisfaction with Social Roles). ResultsTen out of 11 patients agreed to participate (91% response rate). Seizure control at last follow up (median age 25.2 years, range 17.8–29.8 years) was achieved with pyridoxine monotherapy in 70%, 20% with adjunct common-anti epileptic drugs and 10% did not obtain complete seizure control. Neurologic symptoms were present in all but one patient (90%) and included tremors, noted in 40%. Neuro-imaging abnormalities were present in 80%. Intellectual disability was present in 70%. One patient (10%) attended university, three maintained a job without assistance, five maintained a job with assistance or attended social daycare, and one patient never followed regular education. The cohort scored significantly lower on the PROMIS Cognitive Functioning compared to the general (age-related) population. Distribution of scores was wide on all PROMIS item banks. Discussion & conclusionOutcomes of this young adult cohort are heterogeneous and individualized approaches are therefore needed. Long-term seizure control with pyridoxine was achieved for almost all patients. Neurologic symptoms were noted in the majority, including tremors, as well as neuro-imaging abnormalities and intellectual disability, additionally reflected by the PROMIS Cognitive Functioning. PDE-ALDH7A1 patients scored comparable to the general population on all other PROMs, especially regarding Ability to Participate and Satisfaction with Social Roles this may indicate a positive interpretation of their functioning. The aim is to expand this pilot study to larger populations to obtain more solid data, and to advance the use of PROMs to engage patients in research and provide the opportunity for personalized care.

The Effect of Valproate Sodium on the Electrical Activity of Helix aspersa F1 Neurons in a Pentylenetetrazole-Induced Epileptic Model Using an Intracellular Recording System

Background: Epilepsy is a chronic central nervous system disorder with a high prevalence in modern society. Despite using common anticonvulsant drugs, its control is not adequately achieved. Animal models for seizures play the leading role in advancing our understanding of the cellular mechanisms of epilepsy. The present study was an attempt to elucidate the electrophysiological mechanism of the effect of sodium valproate on the cellular model of epilepsy. Understanding the cellular mechanisms of this drug may help clarify the pharmacological screening of other drugs. Methods: The intracellular recording was made from F1 cells of garden Helix aspersa in the presence of Ringer solution. Following the extracellular application of valproate sodium at a concentration of 10 mM after and before the use of (25mM) epileptogenic agent (pentylenetetrazol (PTZ)), we evaluated its effect on paroxysmal depolarization shift (PDS) and electrophysiological characteristics. Results: These results showed that valproate sodium could reduce neuronal excitability. It could significantly hyperpolarize rest action potential by decreasing the frequency of firing rate and increasing the amplitude of afterhyperpolarization (AHP) and can prevent depolarization of rest action potential by PTZ. Conclusions: The results suggested that valproate sodium could reduce the PTZ-induced hyperexcitation by hyperpolarization of resting membrane potential (RMP), a reduction in AHP amplitude, and firing the frequency.

National assessment of anti-epileptic drug exposures among pre-teens and adolescents, 2000–2020

Background and objectives Anti-epileptic drugs (AEDs) are increasingly used to treat psychiatric conditions, exposing many children to potentially harmful medications. This includes adolescents, who are at higher risk for self-harm. The purpose of this study was to describe the epidemiology of pediatric AED poisonings and assess which AEDs are associated with more severe clinical outcomes. Methods This retrospective cross-sectional analysis examined single-substance AED exposure cases in pre-teens (10–14 years) and adolescents (15–19 years) reported to the National Poison Database System (NPDS) between 2000 and 2020 (cases through 2019 were included for trend analysis due to incomplete population data). We described characteristics of ingestions by age group, including AEDs implicated. Results There were 74,818 AED exposure cases reported to the NPDS, including 25,928 (34.7%) in pre-teens and 48,890 (65.3%) in adolescents. Among adolescents, 35,570 (72.8%) exposure cases were intentional, with 27,655 (56.6%) specifically related to a suspected suicide attempt. The most common AEDs implicated in poisonings were clonazepam (19.8%), valproic acid (15.3%), and lamotrigine (13.8%). The odds of hospitalization (adjusted odds ratio [aOR] 2.0 [95% confidence interval [CI], 2.0–2.1]), intubation (aOR 2.1 [95% CI, 1.8–2.4]), seizure (aOR 1.6 [95% CI, 1.4–1.9]), and serious outcome (aOR 1.8 [95% CI, 1.7–1.9]) were higher in the adolescent group compared to the pre-teen group. Intentional ingestions increased by a yearly rate of 2.8% (95% CI, 2.3–3.2). Intentional tiagabine exposure was associated with the greatest increased odds of serious outcome (aOR 4.7 [95% CI, 3.6–6.3]). Discussion In this cross-sectional analysis of pediatric AED exposure cases reported to the NPDS, AED poisonings among pre-teens and adolescents increased significantly between 2000 and 2019. Of particular concern is the large increase in intentional exposure cases related to AEDs. With the population-adjusted rate of epilepsy diagnoses remaining relatively unchanged, these results may indicate that the rise in AED exposure cases may be related to increased prescribing of AEDs for psychiatric indications as opposed to epilepsy. Conclusions Pediatric AED poisonings reported to the NPDS are increasing, especially among adolescents engaging in intentional ingestions. These findings provide additional information for consideration in risk-benefit assessments when selecting medications for the treatment of psychiatric conditions in children.

Free Papers Compiled

Background-Seizure disorder is one of the common disorder in children & adolescents with significant morbidity and mortality. It is associated with other comorbidities. There is limited data regarding seizure disorder and its comorbidities from developing countries.>Aim-Current review aims to study the prevalence and clinicodemographic profile of children and adolescents with seizure disorder along with its comorbidities. It also aims to see the most common antiepileptic drug (AEDs) and add-on AEDs used.Methods-A retrospective chart review was done between Jan’18 to Dec’19 from a child & adolescent clinic in department of psychiatry of a tertiary care center in North India. Variables collected were demographics, clinical presentations, laboratory tests, brain imaging studies, electroencephalography, diagnosis and comorbidities.Results-A total of 839 patients came in the child & adolescent clinic, out of which 158 patients were having seizure disorder with male preponderance. Both the sexes and age groups had generalized tonic-clonic seizures as the most common type of seizures followed by absence seizures & simple partial seizures, myoclonic jerks & complex partial seizures. The commonest comorbidity was intellectual disability followed by ADHD, ASD, depression & BMD. The commonest AED used was sodium valproate and add-on AED used was clobazam followed by other AEDs.Conclusion-The review concludes that GTCS is the most common type of seizure disorder with intellectual disability as the most prevalent comorbidity. Also, sodium valproate and clobazam are the most commonly used AED and add-on AED respectively.

Acute Kidney Injury with Levetiracetam in Patient with Epilepsy: A Case Report

Epilepsy is a common neurological disorder in neurology clinic. Levetiracetam is considered as one of common antiepileptic drugs used to manage epilepsy with good efficacy and tolerability profile. It is renally excreted and not depending on the cytochrome p450. It has adverse effects reported as somnolence, headaches, dizziness, depression and anxiety. Also, it was reported that levetiracetam can cause Acute kidney injury (AKI), renal profile disturbance, that may be related to its way of excretion and possible nephrotoxicity especially with high loading dose. We are reporting a young female patient with epilepsy presented to hospital with status epileptcus and started on loading dose of levetiracetam 3 grams and then maintenance dose of 1 gram twice daily seizure were controlled but she developed acute kidney injury that improved after discontinue leveriracetam and medical management without renal dialysis and discharged home in stable condition. Physician and health care providers should be aware of such rare adverse reaction and available management options for better patient care and outcome.

People with epilepsy and intellectual disability: More than a sum of two conditions

BackgroundAround 25% of people with Intellectual Disability (PwID) have comorbid epilepsy with seizures in up to two-thirds being drug-resistant. Little is known of the general characteristics and prescribing practices to this population. AimDescribe and compare characteristics of two cohorts of PwID and epilepsy in two different countries to inform clinical practice better. MethodAn explorative, retrospective, case-note review in a specialist ID community service in England and in an expert center for PwID and epilepsy in the Netherlands was conducted. Information on ID severity, medical/behavioral/psychiatric/neurodevelopmental/genetic comorbidities, psychotropic, and antiepileptic drugs (AEDs) for each cohort was collected. FindingsThe English cohort consisted of 167 people (98 males; age range 18–73 years; mild/moderate ID- 35%) and the Dutch cohort of 189 people (111 males; age range 18–85 years; mild/moderate ID – 51%). The two cohorts were comparable in their baseline characteristics. The Dutch had higher rates of physical comorbidity, but less mental or behavioral disorders and were more likely to be on anti-psychotic medication. The mean dosages between three most common AEDs prescribed were similar. The most frequently prescribed drug in both centers is valproate. Three-quarters of the Dutch were on three or more AEDs compared to a third in the English cohort. ConclusionsStructured description of the characteristics, differences, and commonalities of PwID, treatment, and services of both countries is presented. This is the first real-world study to reveal unique characteristics of managing epilepsy for a complex ID population. In particular, it highlights the considerable comorbid psychiatric burden and psychotropic prescribing.

VALUE OF P300 AS A SCREENING TOOL OF COGNITIVE IMPAIRMENT IN EPILEPSY: A PROSPECTIVE STUDY FROM INDIA

Objective. Preservation of cognition is essential for good quality life. Epileptic pathological processes and pharmacotherapy are thought to be responsible for the cognitive dysfunction (CDF) in persons with epilepsy (PWE). Regular monitoring of persons on antiepileptic drugs (AED) for CDF is recommended. P300, an attention dependent event related potential (ERP), is known to be abnormal in PWE. The value of P300 in monitoring cognitive functions has not been tested prospectively. Material and methods. PWE not exposed to AED in preceding 6 months were recruited and prescribed one of the three common AEDs i.e. carbamazepine, phenytoin and valproate. Subjective tests of cognition-MoCA, Trail making test, Paragraph memory tests, Stroop test in addition to P300 ERP were administered before initiating AED and repeated after three months on the prescribed AED. The significance of the change in the scores of cognitive tools and P300 latency was ascertained by paired t-test. Outcome. Thirty eight PWE (females 18, mean age mean = 22.89±9.39 yr) qualified the inclusion criterion. The values of P300 latency and deployed subjective tests of cognition at two data collection points were compared with the clinical profile of the patients. Performance of the patients deteriorated on all the cognitive batteries after exposure to AED (mean 107.84±19.2 days). The deterioration was independent of education level, type of AED and seizures. Prolongation of P300 latency from baseline was seen in 30 of 38 patients (78.94%). The sensitivity of P300 for picking cognitive dysfunction was 80.64% taking MoCA scores as a reference. Conclusions. Attention along with several other domains of cognition is affected adversely with AED exposure. The P300 could be useful for monitoring cognitive adverse effects of AED in PWE.

The association of adjusted plasma valproic acid concentration with CYP2C9 gene polymorphism in patients with epilepsy: a systematic review and meta-analysis.

BackgroundValproic acid (VPA) is a common antiepileptic drug used to treat both generalized and partial epilepsy. Although there is increasing evidence to suggest that CYP2C9 gene polymorphisms are associated with interindividual variability of VPA metabolism, the results are debatable. Therefore, in the present study, we conducted a meta-analysis to evaluate the correlation between CYP2C9 gene polymorphisms and adjusted plasma VPA concentration.MethodsThe EMBASE, MEDLINE, and Cochrane Library databases were searched to obtain relevant studies. Eligible articles were reviewed, and data extraction was performed. We calculated 95% confidence intervals (CIs) and mean differences (MDs) to assess the strength of the relationship of CYP2C9 gene polymorphisms with adjusted plasma VPA concentration.ResultsThe meta-analysis included 6 studies involving 847 patients with epilepsy. The pooled analysis showed that the CYP2C9 A1075C (AA vs. AC) polymorphism was related to the adjusted plasma concentration of VPA (P=0.02, I2= 82%). Additionally, the AC phenotype statistically significantly increased the adjusted plasma VPA concentration in children compared with the mixed age subgroup (P=0.04, I2= 48%). A similar association was observed between the AC phenotype for Asians (P<0.00001, I2=0%) but not for Caucasians (P=0.34, I2=87%).DiscussionAge might be a crucial covariate influencing the dosage-adjusted VPA concentration in patients with epilepsy. A reduced VPA dosage may be recommendable for children, particularly Asian children, who are CYP2C9 A1075C AC carriers. Further studies could provide high-quality evidence to confirm the correlation between VPA pharmacokinetics and CYP2C9 A1075C polymorphisms.