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Background: Individual susceptibility to sodium valproate (VPA)-induced tremors may be due to genetic polymorphisms in the gene encoding the uridine diphosphate glucuronosyltransferase (UGT) enzyme, which affec the drug's clinical efficacy and cause toxic side effects. This study aimed to investigate the association between UGT1A6 polymorphisms and VPA-induced tremors in patients with epilepsy., Methods: In total, 128 patients with epilepsy were enrolled. Patients with epilepsy who received VPA were divided into tremor and non-tremor groups. Polymerase chain reaction-restriction fragment length polymorphism was used to investigate the genotype of UGT1A6 polymorphisms., Results: Carriers of the UGT1A6 A541G mutant genotype conferred a higher risk of tremor than wild-type carriers (odds ratio 2.128, P = 0.045). Logistic regression analysis showed that the A541G mutant genotype was a significant genetic risk factor for VPA-induced tremors. This suggests that individual susceptibility to VPA-induced tremors may result, at least partially, from genetic variation in UGT1A6 A541G., Conclusions: Patients with epilepsy carrying the UGT1A6 A541G mutant genotype may have VPA-induced tremors, and early detection of this genotype will help guide the clinical individualizsation of VPA treatment., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: This study aimed to evaluate the impact of prolonged sodium valproate use on bone mineral density (BMD) and Vitamin D levels in pediatric epilepsy patients., Methods: In a cross-sectional study conducted at the Epilepsy Clinic of Niloufer Hospital, Hyderabad, India, 50 pediatric patients (aged 4-10 years) were recruited. The cohort comprised 30 epilepsy patients on sodium valproate treatment (cases) and 20 healthy siblings without epilepsy or valproate use (controls). BMD was assessed using dual-energy X-ray absorptiometry to measure height-adjusted total body less head Z-scores (TBLH Z-scores), and serum 25-hydroxyvitamin D levels were measured. Statistical analysis included independent samples t-tests, Mann-Whitney U tests, and Pearson correlation, with a preliminary power analysis ensuring adequate sample size., Results: Cases exhibited significantly lower BMD TBLH Z-scores (Mean = -1.543) compared to controls (Mean = 0.515, p <.001) and reduced Vitamin D levels (Mean = 9.17 for cases vs. 27.80 for controls, p <.001). A negative correlation was observed between the duration of sodium valproate use and both BMD Z-scores (r = -0.626, p <.001) and Vitamin D levels (r = -0.707, p <.001)., Conclusions: The findings suggest a significant negative impact of prolonged sodium valproate use on both bone density and Vitamin D levels in pediatric patients. These results underscore the importance of monitoring and managing bone health in children receiving long-term sodium valproate therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To evaluate changes in posterior segment parameters in pediatric patients with epilepsy using sodium valproate or levetiracetam monotherapy for at least 12 months., Methods: This study included 45 children with generalized epilepsy aged 6-17 years and 32 age- and gender-matched healthy subjects. The patients were assigned to three groups: Group 1 included patients using valproate monotherapy at a dose of 20-40 mg/kg/day, group 2 included patients using levetiracetam monotherapy at a dose of 20-40 mg/kg/day, and group 3 consisted of healthy controls. Peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell layer-inner plexiform layer (mGCIPL) thicknesses were measured using spectral-domain optical coherence tomography (OCT)., Results: No significant differences were noted between the groups regarding age, gender distribution, visual acuity, spherical equivalent, and intraocular pressure (p > 0.05). The average and temporal, nasal, and superior quadrants RNFL values were significantly thinner in group 1 than in group 2 (p = 0.001, p = 0.023, p = 0.011, and p = 0.001, respectively) and group 3 (p < 0.001, p = 0.032, p < 0.001, and p = 0.001, respectively). The OCT parameters were similar in groups 2 and 3 (p > 0.05). A negative correlation was observed in group 1 between only the average mGCIPL and the treatment dose (r =  - 0.501). In group 2, no significant correlation was found between OCT parameters and the duration of epilepsy treatment, dose of treatment, and age at treatment onset values (p > 0.05)., Conclusion: These findings support that there is an association between sodium valproate treatment and the reduction of RNFL thickness in epilepsy. Levetiracetam treatment appears to be a safe option, but care should be taken regarding ocular side effects that may occur with long-term and high-dose use of sodium valproate., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Aim: To describe the neurodevelopmental phenotype of older children and adults with a diagnosis of Fetal Valproate Spectrum Disorder (FVSD)., Methods: In this cross-sectional study, 90 caregivers were recruited and completed a series of questionnaires regarding the neurodevelopmental outcomes of 146 individuals aged 7-37 years (M = 18.1), including individuals with a formal diagnosis of FVSD (n = 99), individuals exposed to Valproate but without an FVSD diagnosis (n = 24), and individuals not exposed to Valproate (N = 23). The mean dose of valproate exposure for individuals with an FVSD diagnosis was 1470 mg/day., Results: Individuals with a diagnosis of FVSD showed significantly higher levels of moderate (43.4%) and severe (14.4%) cognitive impairment than other groups (p = 0.003), high levels of required formal educational support (77.6%), and poorer academic competence than individuals not exposed to Valproate (p = 0.001). Overall psychosocial problems (p = 0.02), internalising problems (p = 0.05) and attention problems (p = 0.001), but not externalising problems, were elevated in individuals with a diagnosis of FVSD. Rates of neurodevelopmental disorders, particularly autistic spectrum disorders (62.9%) and sensory problems (80.6%) are particularly central to the FVSD phenotype. There was no evidence of a statistical dose-dependent effect, possibly due to the high mean dose of exposure having a uniformly negative impact across the sample. Individuals with FVSD had required a significant number of health and child development services., Interpretation: Children and young adults with a diagnosis of FVSD are at an increased risk of a range of altered neurodevelopmental outcomes, highlighting the need for a multidisciplinary approach to clinical management across the lifespan., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rebecca L. Bromley reports a relationship with UCB Pharma that includes: consulting or advisory. Laura M. Yates reports a relationship with Sanofi Genzyme South Africa that includes: consulting or advisory., (Copyright © 2023. Published by Elsevier Inc.)

Background: Fanconi syndrome (FS) can be of primary or secondary origin. Some cases of FS secondary to the use of sodium valproate (VPA) have been described, mostly in children with severe psychomotor retardation who are fed by feeding device. The objetive of this study was to describe patients treated for this entity in our center, comparing them against the published literature., Methods: Descriptive study of our patients and those found in the literature. Epidemiologic and clinical data were collected., Results: We describe seven patients (three to 17 years old) with severe psychomotor retardation and undergoing treatment with VPA. Four presented pathologic fractures before the diagnosis of FS, and in three patients the diagnosis was reached due to abnormal laboratory findings. A review of the published cases was carried out and, including our sample, a total of 42 patients were studied: 51.3% were male, and the median age at diagnosis of FS was 6 years. Severe psychomotor retardation was found in 92.8% of patients, 78% carried a feeding device, and 77.5% received treatment with several antiepileptic drugs. The mean duration of VPA treatment was 5.7 years (range 2 to 7.5 years). Fifteen patients (37.5%) had bone complications. The resolution time of FS after discontinuation of drug therapy ranged from two to 19 months (median 4 months)., Conclusions: FS related to VPA is a rare complication, but it should be considered in patients with epilepsy, especially if they have severe psychomotor retardation, are users of feeding devices, and receive other antiepileptic treatments in addition to VPA., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To estimate the safety and efficacy of sodium valproate combined with levetiracetam in paediatric patients with epilepsy based on randomized controlled trials (RCTs)., Methods: The Cochrane Library, PubMed, Web of Science, Chinese Journal Full-Text Database (CNKI), WANGFANG DATA and Sino Med were searched between January 1946 and May 2021. The included literature was randomized controlled clinical trials focusing on sodium valproate combined with levetiracetam in paediatric patients with epilepsy. Two evaluators separately collected the data based on the retrieval strategy, filtered the literature in accordance with the inclusion and exclusion criteria, and summarized the literature that satisfied the criteria. The statistical programme used for the meta-analysis was Stata V14.0., Results: Of 577 original titles screened, data were extracted from 7 studies (617 participants). Compared with sodium valproate alone or sodium valproate combined with topiramate, the application of sodium valproate combined with levetiracetam in the treatment of paediatric epilepsy significantly improved the overall therapeutic effect (RR=1.24, 95% CI: 1.16 to 1.33, p=0.927). The observation group significantly reduced the occurrence of adverse drug reactions (ADRs) (RR=0.54, 95% CI: 0.37 to 0.79, p=0.602). Egger's regression test of the overall therapeutic effect showed no potential publication bias (p=0.122)., Conclusion: Based on this meta-analysis, compared with sodium valproate alone or sodium valproate with topiramate, the application of sodium valproate combined with levetiracetam in the treatment of paediatric epilepsy can significantly improve the overall therapeutic effect and simultaneously reduce the occurrence of ADR. Therefore, we recommend sodium valproate combined with levetiracetam for the therapy of paediatric patients with epilepsy., (Copyright © 2021 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background: Epilepsy is a long-term recurrent chronic brain disease that can cause significant emotional burden to the patient and their family, as well as huge economic costs to society. Timely and accurate diagnosis of epilepsy, together with early and standardized treatments can effectively control seizures and restore the patient's quality of life and reduce the economic burden. This meta-analysis examined the efficacy of lamotrigine administration in patients with epilepsy., Methods: A literature search was performed in the PubMed, Embase, and OVID-Medline databases to identify articles related to epilepsy and lamotrigine that were published from the establishment of the database to April 2021. The keywords used for the literature search included "epilepsy", "sodium valproate", "lamotrigine", "effectiveness", and "therapeutic effect". It uses Cochrane review manual 5.3 to evaluate the quality of the included literature and review manager 5.3 software for meta-analysis., Results: A total of 9 studies involving 1,864 patients with epilepsy were included in this meta-analysis. The results revealed that, after treatment failure with the first drug of valproic acid, the total effective rate of lamotrigine treatment had an odds ratio (OR) of 2.21 with a 95% confidence interval (CI) of 1.15 to 4.27 (Z=2.37; P=0.02). The total adverse reaction rate (OR =0.70; 95% CI: 0.55 to 0.88; Z=2.98; P=0.003) and the improvement rate of epilepsy associated with lamotrigine treatment (OR =4.22; 95% CI: 1.00 to 17.84; Z=1.96; P=0.05) were all significantly higher than that of other drug treatments., Discussion: A total of 9 articles were included in this meta-analysis to examine the efficacy of lamotrigine in the treatment of epilepsy. The clinical efficacy of lamotrigine addition therapy was found to be superior to lamotrigine replacement therapy, and the incidence of adverse reactions was lower than that of lamotrigine replacement therapy. However, due to the low methodological quality of the included literatures, this conclusion should be further verified using large sample and high-quality randomized double-blinded experiments.

Epilepsy is a common chronic neurological disease that manifests as recurrent seizures. The incidence and prevalence of epilepsy in women are slightly lower than those in men. Polycystic ovary syndrome (PCOS), a reproductive endocrine system disease, is a complication that women with epilepsy are susceptible to, and its total prevalence is 8%-13% in the female population and sometimes as high as 26% in female epilepsy patients. The rate of PCOS increased markedly in female patients who chose valproate (VPA), to 1.95 times higher than that of other drugs. In addition, patients receiving other anti-seizure medications (ASMs), such as lamotrigine (LTG), oxcarbazepine (OXC), and carbamazepine (CBZ), also have reproductive endocrine abnormalities. Some scholars believe that the increase in incidence is related not only to epilepsy itself but also to ASMs. Epileptiform discharges can affect the activity of the pulse generator and then interfere with the reproductive endocrine system by breaking the balance of the hypothalamic-pituitary-ovarian (HPO) axis. ASMs may also cause PCOS-like disorders of the reproductive endocrine system through the HPO axis. Moreover, other factors such as hormone metabolism and related signalling pathways also play a role in it., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Zhang, Wei, Tai, Yu and Xu.)

Objectives: The aim of this study was to compare the adherence, healthcare resource and cost implications of using Episenta® minitablets or Epilim® monolithic tablet in the treatment of epilepsy in children in England., Design: This is a retrospective analysis of healthcare administrative databases., Setting: The study analysed data collected from Primary Care (Clinical Practice Research Datalink (CPRD)) and Secondary Care (Hospital Episode Statistics (HES)) in England, UK., Participants: Patients (stratified by age 0-12; 0-17 and 18+ years) with a diagnosis of epilepsy in receipt of a new prescription for Episenta® minitablets or Epilim® monolithic tablet from January 2012 to October 2017. Limited to those with a minimum of 12 months follow-up., Main Outcome Measures: Determining the impact of sodium valproate formulation on measures of treatment adherence and healthcare resource usage., Results: There were 793 patients in the dataset: 84 on Episenta® minitablets and 709 on Epilim® tablets. Measures of medication adherence were not significantly different between the minitablet formulation and the monolithic matrix tablet. However there was a greater annualised incidence rate of epilepsy related primary healthcare contacts in a paediatric population from the tablet formulation compared to those treated with minitablets (95% CI [-1.561,0.0152]) for those aged 0-12 and (95% CI [-1.3234,-0.0058]) for those aged 0-17. This is found despite a lower dose being used in the minitablet cohort (595 mg vs 945 mg for the tablet) for those aged 0-17 which indicates effective therapy at a lower dose using the minitablet compared to the monolithic tablet formulation., Conclusions: Minitablet formulations of sodium valproate (presented as granules in capsules or sachets) can provide better therapeutic outcomes and reduced associated healthcare resource costs compared to monolithic tablets in children and young people with epilepsy. The interpretation of this data is limited by the large difference in sample size between the two groups which needs additional investigation to generate matched data for future comparisons. Further work is required to understand why the Episenta® minitablets formulation generated better outcomes in paediatric populations., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The UK Medicines and Healthcare products Regulatory Agency (MHRA) published guidelines restricting the use of sodium valproate in women of childbearing age unless they consented to the pregnancy prevention programme (PPP), receiving counselling by an epilepsy specialist, or meeting exclusion criteria., Methods: We contacted every woman of childbearing age on valproate for epilepsy in NHS Tayside (122)., Results: Seventeen out of 122 (13.9%) responded to the initial invitation to attend, and 25 out of 122 (20.4%) responded to a letter sent to their GP. Twenty-five attended, 21 completed a consent form, seven switched to another drug and three attended to express dissatisfaction with the MHRA guidance. There were 53 patients identified with learning difficulties. Consent was only taken from three patients, with carers declining to sign consent because the patient was not sexually active., Conclusion: Our study suggests that patients and carers do not wish to stop valproate or engage in PPP despite being made aware of MHRA guidance., Competing Interests: Dr Morrison reports grants and personal fees from UCB and GSK, grants and personal fees from Eisai and grants from Cyberonics, during the conduct of the study. Dr White is a commercial research champion for NHS Tayside, receiving one paid session a week to do commercial research. She has not received any direct funding from pharmaceutical companies in the last 36 months.

Background: We sought to explore the effects of sodium valproate combined with lamotrigine on quality of life and serum inflammatory factors in patients with poststroke secondary epilepsy., Methods: A total of 145 patients with post-stroke secondary epilepsy admitted to our hospital from January 2017 to June 2018 were collected: 76 treated with sodium valproate combined with lamotrigine (study group) and 69 patients treated with sodium valproate alone (control group). The levels of serum high-mobility group protein B1, matrix metalloproteinase 9, and interleukin 6 were detected before and after treatment, and the therapeutic efficacy and adverse reactions were compared between the 2 groups., Results: The total effective rate of the study group was higher than that of the control group. Both groups decreased in epileptiform discharges or in the number of involved leads after treatment, with the results of the study group being lower than those of the control group. The quality of life scores in both groups was increased after treatment, albeit the scores of the study group were higher than those of the control group. In terms of the levels of serum inflammatory factors, the 2 groups were reduced after treatment; the levels of the study group were lower than those of the control group. Regarding the incidence of adverse reactions, no significant difference was seen between the 2 groups., Conclusions: Sodium valproate combined with lamotrigine has better clinical efficacy and higher safety in the treatment of poststroke secondary epilepsy and is able to reduce the expression levels of serum inflammatory factors., Competing Interests: Conflict of Interest The authors declare that they have no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

A 22-year-old female was admitted to our hospital due to acute onset of severe headache, confusion, and deterioration of consciousness. Results of initial examinations did not suggest cerebrovascular diseases, encephalitis, or nonconvulsive status epilepticus. Over the next several weeks, her level of consciousness fluctuated in parallel with the severity of headache. The electroencephalogram, recorded during a symptomatic episode, showed lack of posterior dominant rhythm, and the single-photon emission CT (SPECT) also revealed a decrease in cerebral blood flow predominantly in the occipital lobes. Administration of sodium valproate and topiramate, recommended as treatment for migraine, dramatically ameliorated her headache and consciousness. Although this was an adult-onset case, her symptoms and clinical course were similar with the diagnosis of ICHD-3-unlisted confusional migraine rather than other listed subtypes of migraine with aura. Further accumulation of similar adult-onset cases is necessary to clarify the nature of this illness.

Background and Purpose: Efficacy of sodium valproate in epilepsy is limited by its poor blood brain barrier penetration and side effects. Nanoparticles may offer a better drug delivery system to overcome these limitations. This study evaluated the efficacy of sodium valproate encapsulated in nanoparticles in pentylenetetrazole (PTZ) induced acute and kindling models of seizures in male Wistar rats., Methods: Poly lactic-co-glycolic acid (PLGA) based, polysorbate 80 stabilized sodium valproate loaded nanoparticles (nano sodium valproate) and rhodamine loaded nanoparticles (RLN) were formulated by double emulsion- solvent evaporation method and characterized for their size, shape, zeta potential and drug loading percentage. RLN was used to demonstrate blood brain barrier (BBB) permeability of nanoparticles. Serum drug levels were estimated using high performance liquid chromatography. The efficacy of standard sodium valproate (300 mg/kg) and nano sodium valproate (∼300, ∼150 and ∼75 mg/kg of sodium valproate) were evaluated in experimental animal models of seizures along with their effects on behavioral and oxidative stress parameters. Drugs were administered 60 min before PTZ in acute model. In the kindling model, drugs were administered every day while PTZ was administered on alternate days 60 min after drug administration. All the study drugs/compounds were administered intraperitoneally., Results: RLN were observed to be clustered in cortex which implied that the nanoparticles crossed BBB. Both standard sodium valproate and nano sodium valproate reached therapeutic serum level at 15 min and 1 h, but were undetectable in serum at 24 h. In acute PTZ (60 mg/kg) model, nano sodium valproate (∼300 mg/kg of sodium valproate) and standard sodium valproate showed protection against seizures till 6 h and 4 h, respectively. There were significant behavioral impairment and oxidative stress with standard sodium valproate in acute model as compared to nano sodium valproate at 6 h. In kindling model, induced with PTZ (30 mg/kg, every alternate day for 42 days), complete protection from seizures was observed with nano sodium valproate (∼150 mg/kg and ∼75 mg/kg of sodium valproate) and standard sodium valproate (300 mg/kg). Similarly, significant protection from behavioral impairment and oxidative stress was observed with standard sodium valproate and nano sodium valproate as compared to PTZ., Conclusion: When compared to conventional therapy, nano sodium valproate showed protection from seizures at reduced doses and for a longer duration in animal models of epilepsy. This study suggests the potential of nano sodium valproate in the treatment of epilepsy., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: Phenobarbital and sodium valproate are broad spectrum and inexpensive antiepileptic drugs that are used to treat convulsive epilepsy. We examined the therapeutic effects of phenobarbital and sodium valproate in patients with convulsive epilepsy in the rural northeast China, and discuss our efforts to ensure patients' compliance., Methods: Patients with convulsive epilepsy were screened by trained township health center doctors. Patients in the phenobarbital group were enrolled between January 2011 and December 2012, and followed up until December 2017. Patients in the sodium valproate group were enrolled between January 2011 and December 2017, and followed up for 1 year. Efficacy of phenobarbital or sodium valproate was assessed by the reduction in seizure frequency., Results: A total of 1200 patients were diagnosed by screening and rechecking, of which 925 patients received phenobarbital and 275 received sodium valproate. In the phenobarbital group, 528 patients were followed up for ≥60 months, and the efficacy rates of reduction of seizure frequency by at least 75% was in the fifth year. In the sodium valproate treatment group, 228 patients were followed up for 12 months, and the reduction of seizure frequency by at least 75% was 60.4%. 444 patients (37%) did not complete the study. Dizziness (27%) was a common adverse event in phenobarbital group. In the sodium valproate group, gastrointestinal complaints (27.3%) was a common adverse event., Conclusion: Phenobarbital and sodium valproate were proven to be efficacious in treating convulsive epilepsy in rural northeast China. The patients' compliance still needs to be improved., (Copyright © 2019 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background: Valproic acid (VPA) is one of the commonly used antiepileptic drug. It has various side effects which may be fatal, such as fulminant hepatitis. Nocturnal enuresis (NE) has rarely been reported as side effect of VPA. The aim of this study is to evaluate the frequency of VPA-induced NE and discuss the possible reasons., Materials and Methods: This retrospective cohort study was performed at the Department of Pediatric Neurology, Eskisehir Osmangazi University Hospital, in Eskisehir, Turkey, between April 2014 and April 2015. The patient population was generated from the epilepsy patients who were receiving VPA monotherapy. Control group population was generated from nonepileptic patients who visited our clinic for headache. Age range of the patients and the control group was determined to be 5-15 years., Results: The patients group consisted of 189 (53.7%) boys and 163 (46.3%) girls and mean age of the patients was 9.1 ± 3.02 (5-15) years. The control group consisted of 92 (51.1%) girls and 88 (48.9%) boys and mean age of the patients was 8.75 ± 3.23 (5-15) years. We found the incidence of VPA-induced NE to be 5.7%. In the control group, incidence of NE was found to be 10.7%., Conclusion: This study is one of the largest series about VPA-induced NE. NE is a side effect of VPA that is generally overlooked by clinicians and slightly less well-known too. The literature on VPA-induced NE is very inadequate, and its etiology is not clear. In our study, we did not detect renal dysfunction in the patients with VPA-induced NE; therefore, we may speculate that the NE was caused by the increased sleep depth with VPA treatment. We believe that larger prospective studies including polysomnography may be helpful to shed light on the cause of VPA-induced NE., Competing Interests: There are no conflicts of interest.

GABA is a dominant inhibitory neurotransmitter in the brain and A type GABA receptor (GABA A R) phosphorylation is critical for GABA-mediated inhibitory effect. However, its role in the neuroprotective effect of sodium valproate (VPA), a prevalent drug for treating patients with epilepsy, remains elusive. The present study was conducted to explore the role of GABA A R phosphorylation in the neuroprotection of VPA against a kainic acid-induced epileptic rat model and the potential molecular mechanisms. Neuronal apoptosis was evaluated by TUNEL assay, PI/Annexin V double staining, caspase-3 activity detection and Bax and Bcl-2 proteins expression via Western blot analysis. The primary rat hippocampal neurons were cultivated and cell viability was measured by CCK8 detection following KA- or free Mg 2+ -induced neuronal impairment. Our results found that VPA treatment significantly reduced neuronal apoptosis in the KA-induced rat model (including reductions of TUNEL-positive cells, caspase-3 activity and Bax protein expression, and increase of Bcl-2 protein level). In the in vitro experiments, VPA at the concentration of 1 mM for 24 h also increased cell survival and suppressed cell apoptosis in KA- or no Mg 2+ -induced models via CCK8 assay and PI/Annexin V double staining, respectively. What is more important, the phosphorylation of γ2 subunit at serine 327 residue for GABA A R was found to be robustly enhanced both in the KA-induced epileptic rat model and neuronal cultures following KA exposure after VPA treatment, while no evident alteration was found in terms of GABA A R β3 phosphorylation (408 or 409 serine residue). Additionally, pharmacological inhibition of protein kinase C (PKC) clearly abrogated the neuroprotective potential of VPA against KA- or free Mg 2+ -associated neuronal injury, indicating a critical role of PKC in the effect of GABA A R γ2 serine 327 phosphorylation in VPA's protection. In summary, our work reveals that VPA mitigates neuronal apoptosis in KA-triggered epileptic seizures, at least, via augmenting PKC-dependent GABA A R γ2 phosphorylation at serine 327 residue.

Competing Interests: Competing interests: None declared.

Purpose: To understand the preconception experiences of women with epilepsy who have been taking the teratogenic drug valproate., Methods: Seven women were recruited, three from a preconception clinic and four from an antenatal clinic in a region of the UK. All had taken valproate preconceptionally. Three preconception clinic encounters were observed and audio-recorded. Interviews with all women were analysed using Interpretative Phenomenological Analysis (IPA)., Results: Women experienced a "trajectory of balance". Women moved from "maintaining balance" by using valproate to control seizures, to a "shattering of harmony" at the prospect of changing medication and as a result of the physical and mental effects of changing medication, to "restoring balance" which could involve "a new self" due to dramatic changes. Women balanced their health needs with those of their baby, and took responsibility for medication decision-making. They found it difficult to see "who is looking after me" in the healthcare system, either to access preconception care, or to support them through the stress of changing medication. Their journey ended with coming to terms with a variety of experiences: choosing not to have a baby due to unsuccessful change from valproate, recognising that a child from a previous pregnancy had been harmed by valproate or that the current pregnancy might be at risk, or successful medication change in preparation for pregnancy., Conclusion: A clear and adequately funded preconception care pathway is needed from epilepsy diagnosis, including support for stress. Understanding what influences maternalisation may help understand uptake of preconception care., (Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: To explore the risk factors for the development of sodium valproate (VPA)-induced renal tubular dysfunction for early diagnosis and treatment., Study Design: The subjects were selected from patients who were diagnosed with epilepsy and administered VPA. Blood and spot urine samples were collected and measured the concentration of VPA, the level of serum phosphorus, serum uric acid, serum free carnitine, serum cystatin-c, and urine β2-microglobulin (BMG). Patients with urine BMG/creatinine levels above 219.2 were treated as renal proximal tubular dysfunction (RTD), with all others treated as non-RTD., Results: Eighty-seven patients, 4-48 years, 53 men and 34 women, were studied. RTD group is 17 patients and non-RTD group is 70 patients. Univariate analyses revealed that the RTD patients were more likely to be bedridden, receiving enteral tube feeding, taking more anticonvulsants, and demonstrating significantly lower serum levels of free carnitine, uric acid, and phosphorus. Among them, bedridden, free serum carnitine, and phosphorus levels were associated with the development of RTD by multivariate analysis., Conclusions: Bedridden patients receiving VPA are susceptible to hypocarnitinemia, which can cause RTD and may lead to FS. Therefore, urinary BMG should be measured regularly in all patients receiving VPA to assess renal tubular function. An additional measurement of serum free carnitine level should be considered in patients who developed RTD. Supplementation of carnitine for those patients to prevent such complication deserves for further study.

Objectives: The aim of this study was to investigate the effect of carbamazepine (CBZ) and sodium valproate (VPA) monotherapy on sexual functions, sex hormones, and semen analysis and quality in male patients with epilepsy., Methods: A total of 59 male patients with epilepsy, of which 30 were on VPA monotherapy and 29 were on CBZ monotherapy, were included in the study between January 2015 and March 2016. A control group was established with 30 healthy males. Luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), free testosterone (fT), estradiol (E2), sex hormone-binding globulin (SHBG) levels and bioactive testosterone (BAT)/bioactive estradiol (BAE), and BAT/LH ratio were studied in groups. All groups received semen analysis and International Index of Erectile Function Scale (IIEF-5) test for erectile dysfunction., Results: E2 and DHEAS levels were higher in VPA and CBZ groups compared to control group (P < .001, P = .014). The decrease in fT levels in the VPA group was statistically significant (P = .038). No significant difference was detected in levels of SHBG, LH, and FSH (P > .05). BAT/BAE ratios were low both in VPA and CBZ groups (P < .001; P < .001), while BAT/LH ratios were low only in CBZ group (P = .033). In semen analysis, semen volume and number of normal sperms were found to be significantly lower in patients receiving antiepileptic drugs compared to control group (P < .05). There were no differences between the groups in rates of abnormal sperm morphology. IIEF-5 scores were found to be significantly lower in VPA and CBZ groups (P < .001)., Conclusion: VPA or CBZ therapy may lead to dysregulation of sex hormones, sexual dysfunction, and alterations in semen analysis in male patients with epilepsy. This must be considered for the selection of antiepileptic drugs in young male patients., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: This study aims to describe the incidence of adverse drug reactions (ADRs) in children receiving antiepileptic drugs (AEDs) and compare ADRs to the individual drugs when given as monotherapy., Method: Paediatric patients (≤18 years old) were enrolled for this prospective observational study over a 6-month period, between September 2015 and March 2016. Adverse reactions to antiepileptic drugs (AEDs) were elicited at the time of enrolment and after 3 months using the Paediatric Epilepsy Side Effects Questionnaire., Results: A total of 1139 suspected ADRs were reported in 124 participants. Eighteen different AEDs were prescribed. Sixty-six children (53%) were receiving AED monotherapy at the time of recruitment; 34/66 (52%) of whom received new generation AEDs. Levetiracetam was the most frequently prescribed AED (62/124, 50%). When only children receiving AED monotherapy were considered, fatigue, drowsiness, weight gain, dizziness were less likely with levetiracetam (p < .01). Slow thinking and decreased concentration were less likely with levetiracetam or carbamazepine than valproic acid (p < .05). Five patients (four on polytherapy) discontinued AED treatment due to ADRs and 2 had a dose reduction., Conclusions: Levetiracetam and carbamazepine were better tolerated than sodium valproate., (Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background: Polycystic ovary syndrome (PCOS) is a common ovulatory disorder that can be induced by sodium valproate (VPA)., Patient: We report a case of PCOS that developed in a 15-year-old girl with idiopathic epilepsy after she took VPA. VPA administration stopped her seizures, but it also led to weight gain and amenorrhea, and the patient was diagnosed with PCOS on the basis of diagnostic imaging and serological examination results. Cessation of VPA administration led to reduced weight gain and restored menstruation., Conclusions: The risk of PCOS developing in patients with epilepsy is known to be high, and the association of VPA with PCOS is well established, so if physicians feel this is the best drug to prescribe for female patients with epilepsy, they should carefully monitor the patients' weight and menstruation, and immediately perform ovarian imaging and hormonal examinations if any abnormalities are observed.

Purpose: Excessive weight gain associated with sodium valproate (VPA) may predispose patients with epilepsy to other health problems such as insulin resistance. We prospectively evaluated the long-term impact of VPA monotherapy compared with lamotrigine (LTG) monotherapy on anthropometric and metabolic parameters in women with epilepsy. Our primary objective is to understand the underlying mechanism responsible for VPA-induced obesity., Methods: Sixty-six female patients with newly diagnosed or untreated epilepsy were included in the study. Thirty-four patients with VPA and thirty-two patients with LTG were treated for a period of one year in our center. Anthropometric and clinical data were collected at 5 time points: before, at 6th week, 3rd month, 6th month, 9th month and 12th month (last visit). Biochemical and hormonal data were collected 2 time points: before and last visit., Results: Subjects in the VPA group had significantly higher body weight than LTG-treated subjects (64.88±3.25 vs. 58.28±2.43, P<0.001). HOMA-IR level was significantly increased (2.76 vs. 1.35, P<0.05), and adiponectin levels were significantly lower in the VPA group (3.46 vs. 6.22, P<0.05). Triglycerides levels were significantly increased (118 vs. 96, P<0.05), and HDL-C levels were significantly lower in the VPA group. Both the VPA-treated group and the LTG-treated group showed no significant difference in term of total cholesterol, LDL-C, fasting blood glucose and serum leptin levels., Conclusions: Based on the findings of this study, we proposed that VPA induced hypoadiponectinemia which correlates significantly with insulin resistance. These two factors may be responsible for weight gain, possible by stimulating appetite. Valproic acid appears to be use cautionally in obese females with epilepsy., (Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: Lamotrigine (LTG) is a broad-spectrum antiepileptic drug that is widely used in clinic. However, the effect of LTG on cognition and neurodegeneration during epilepsy treatment remains controversial. In this study, we compared the cognitive effects of LTG and sodium valproate in pentylenetetrazole (PTZ)-kindled animal model, and the dose dependency was tested for LTG., Methods: PTZ-kindled animals were divided into the following treatment groups: control group, treated with 3.5 mL/kg of 0.9% sodium chloride; low-dose LTG group, treated with 12.5 mg/kg of LTG; middle-dose LTG group, treated with 25 mg/kg of LTG; high-dose LTG group, treated with 50 mg/kg of LTG; VPA group, treated with 300 mg/kg of VPA. The Morris Water Maze (MWM) test commenced from the 10th day of treatment. Hippocampal cell apoptosis was determined by TUNEL staining after two weeks of treatment., Results: Compared to the vehicle-treated control group, escape latency was significantly reduced in the middle- and high-dose LTG- and VPA-treated groups on the 3rd and 4th day of the MWM test (p < .05), and spatial probe frequency was significantly improved in the middle- and high-dose LTG- and VPA-treated groups (p < .05). Furthermore, the immunohistochemical score of TUNEL positive cells significantly decreased in the hippocampal CA1 region in the middle- and high-dose LTG- and VPA-treated groups (p < .05)., Conclusion: Our data suggests that LTG may ameliorate epilepsy-induced cognitive impairment and neuronal cell apoptosis during epilepsy treatment. LTG may ameliorate cognitive impairment and neuronal cell apoptosis during epilepsy treatment., (© 2016 The Authors Synapse Published by Wiley Periodicals, Inc.)

Epilepsy is a chronic neurological disease affecting more than 69 million people worldwide, nearly 90% of them in low and middle-income countries (LMICs). In those countries, only four major antiepileptic drugs are commonly used: phenobarbital, carbamazepine, sodium valproate and phenytoin. There are also problems with the accessibility, availability and quality of drugs. The main objective was to review the literature concerning "long" sustained-release formulations of AEDs that have the potential to reduce the number of administrations and help overcome problems of compliance, accessibility and the treatment gap. The main endpoint was a releasing of the active ingredient over more than 24h. We also assessed the feasibility and acceptability in resource-limited settings. Two drugs were found in unconventional release formulations: carbamazepine and sodium valproate; but they were not "long" sustained release because they required administration once a day. Several techniques were available, including: esterification, transdermal devices, liposomes and polymeric devices preformed or formed in situ. In situ methods for the preparation of injectable biodegradable microparticles or implants for controlled delivery seemed best suited to the objective. Furthermore, they appear to fulfil the requirements of feasibility and cost. Sodium valproate appeared as well to be a relevant candidate for a "long" sustained release formulation that would improve access to medicines for people with epilepsy in resource-limited settings. ., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The effects of the antiepileptic drugs sodium valproate (VPA) and levetiracetam (LEV) on reproductive endocrine function, sexual function, and spermatozoa were explored, together with their possible etiological mechanisms, in Chinese Han men with epilepsy. Following VPA treatment (n=32), luteinizing hormone and follicle-stimulating hormone levels were significantly lower than in controls (n=30). The bioactive testosterone/luteinizing hormone ratio and the prolactin level were significantly elevated in the VPA treatment group. There were no significant differences in these hormones between the LEV treatment (n=20) and control groups. The rates of sperm morphologic abnormality (head, body, and tail) were significantly higher in the VPA treatment group than the control group but did not differ significantly between the LEV treatment and control groups. The sperm motility rate was significantly lower in the VPA treatment group (grade A sperm motility rate <25%, grade A+B sperm motility rate <50%) than in controls, as well as in the LEV treatment group (grade A sperm motility rate <25%). Patients in the VPA and LEV treatment groups had lower scores on questions 1, 2 and 3 of a simplified International Index of Erectile Function Scale than controls, but no significant difference on questions 4 or 5. The total International Index of Erectile Function Scale scores were significantly lower in the VPA and LEV treatment groups. We conclude that treatment with VPA adversely affects reproductive endocrine function, sperm parameters and sexual function to varying degrees in Chinese men with epilepsy., (Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.)

Objective: Epilepsy affects over 1% of the global population. Polypodium vulgare L. has emerged in studies, suggesting its potential antiepileptic effect. This study evaluated the anticonvulsant efficacy of the hydroalcoholic extract of Polypodium vulgare L. in a pentylenetetrazole (PTZ)-induced epilepsy model in rats. This research aimed to determine the optimal dosage for delaying seizure onset and reducing seizure severity. This study investigated whether the active compounds offer a viable alternative for epilepsy management, mainly through their potential interaction with GABAergic mechanisms. Methods: We randomly selected four groups of 10 and 2 groups of 8 male Wistar laboratory rats. The reference and control groups received PTZ and distilled water, respectively. In contrast, experimental groups 1 and 2 received the hydroalcoholic extract of Polypodium vulgare L. at doses of 300 and 500 mg per kg of body weight. Experimental groups 3 and 4 received 150 and 300 mg per kg dose. Chemical kindling was induced in all groups via intraperitoneal injection of PTZ. Data analysis was conducted using Statistical Package for the Social Sciences version 20 software. Results: The hydroalcoholic extract of Polypodium vulgare L. exerted a pronounced mitigating effect on convulsions induced by PTZ administration, specifically at a dosage of 300 mg/kg of body weight. It effectively prolonged the time necessary for seizure onset. Conclusion: The administration of a 300 mg dose of the hydroalcoholic extract of Polypodium vulgare L. demonstrated superior efficacy compared with its 500 mg counterpart and both the 300 and 150 mg doses of sodium valproate in addressing PTZ-induced epilepsy. The results suggest that the hydroalcoholic extract of Polypodium vulgare L. has promise as an effective treatment for epilepsy. [ABSTRACT FROM AUTHOR]

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Long-term therapy with antiseizure medications (ASMs) has been associated with metabolic consequences that lead to an increase in the risk of atherosclerosis in patients with epilepsy. This study was conducted to assess the effects of ASMs on vascular risk factors namely, serum Lipid profile and C-reactive protein (CRP) in epileptic patients and to assess the correlation between the duration of the ASMs, and carotid intima media thickness (IMT). Forty three adult patient participants who were receiving ASM monotherapy for more than 2 years and 43 control patients were enrolled in this study. All participants received measurement of common carotid artery (CCA) and IMT by B-mode ultrasonography to assess the extent of atherosclerosis. Other measurements included body mass index (BMI), serum lipid profile and CRP. The correlation between duration of ASM and average carotid IMT was calculated by using the Pearson's correlation coefficient method. The majority of subjects on phenytoin 8 (66.7%) were positive for CRP. There was an equal proportion of patients on carbamazepine who were equally positive 5(50%) and negative 5(50%) for CRP. There was a statistically significant association between phenytoin consumption and CRP positivity. There was positive correlation between duration of phenytoin consumption and average IMT. There was a strong positive correlation between duration of phenobarbitone consumption and average IMT and was statistically significant. Our results also suggest that long-term use of ASMs with prominent effects on the enzyme system, including Carbamazepine, phenytoin, sodium valproate or phenobarbitone may contribute to the progression of atherosclerosis in patients with epilepsy.

Background Epilepsy is a chronic episodic brain disorder with a high incidence and can seriously affect the quality of life of the patients. Therefore, timely treatment to control seizures is particularly important. Numerous studies have shown the effect of antiepileptic drugs on cognition, but there are few studies on the effects of different functional areas in children. Objective To explore the effects of sodium valproate (VPA) , oxcarbazepine (OXC) and levetiracetam (LEV) on the development of different functional areas in children with focal epilepsy by Griffiths Development Scales-Chinese Edition (GDS-C) . Methods A total of 83 children with focal epilepsy who attended in outpatient and ward of the Department of Pediatric Neurology of the Third Affiliated Hospital of Zhengzhou University for the first time from January 2021 to April 2022 were selected, and randomly divided into VPA group (n=27) , OXC group (n=28) and LEV group (n=28) according to the random number table method, 30 healthy children who were examined during the same period were selected as the control group. The changes of EEG interictal epileptiform activity (IEA) before and after 6 months of treatment were recorded and the clinical effect was evaluated according to seizure frequency, the GDS-C was used to evaluate the development quotient of each functional area in the children. Results The total clinical effective rates of VPA group, OXC group and LEV group were 92.6%, 89.3% and 92.9%, with no significant difference among the three groups (χ2=0.418, P=1.000) . The total EEG IEA effective rate of the VPA group, OXC group and LEV group were 88.9%, 57.1% and 89.3%, with significant differences among the three groups (χ2=11.152, P=0.004) ; the total effective rate of EEG IEA in OXC group was lower than that in VPA group and LEV group (P

Background Neurological disorders (ND) affect the structure and function of the central nervous system, including Alzheimer's and Parkinson's diseases, epilepsy, migraine and stroke. ND has major symptoms ranging from mild to severe memory problems and physical disabilities. The present study investigated central nervous system (CNS) drug utilization trends, drug–drug interaction and morbidity patterns in ND. Methods A prospective study was carried out at a multi-specialty hospital, including neurology outpatient cases, in 2016. A study was ethically approved by the institutional ethics committee (IEC) for human research, and data were collected from patients' case records. The prescribing trend was assessed by World Health Organization (WHO) core prescribing indicators. The International Classification of Diseases (ICD) 10 was used to assess the morbidity pattern. Drug–drug interactions were analysed by a multidrug interaction checker. Results We discovered that 53.57% and 46.42% of the 280 neurology cases were female and male, respectively. Here, we showed that epilepsy was the most commonly diagnosed (31.07%) condition, followed by migraine (30.35%), Parkinsonism (Pn) (13.21%), Alzheimer's and dementia (AD) (10.71%) and myasthenia gravis (7.14%). The most commonly used CNS drugs were sodium valproates. Donepezil, fluoxatin and levodopa–carbidopa. In this study, 80% of drugs were prescribed with the most common category being antiepileptics; 16.77% and 23.21% of prescriptions observed potential drug–drug interactions. Conclusions The treatment priority for epilepsy was sodium valproate, which had a high prescription rate. For AD, donepezil was given priority, while in PN, levodopa–carbidopa was prescribed most often. In significant drug–drug interactions (DDI), pharmacodynamic mechanisms were very common, while in minor DDI, pharmacokinetic mechanisms were observed. [ABSTRACT FROM AUTHOR]

This study aimed to carry out a comparative study of the main models of chronic epilepsy induced by pentylenetetrazole (PTZ)-kindling method and to assess the efficacy of sodium valproate, one of the main antiepileptics, on the best epilepsy-inducing kindling model. Two sets of 24 animals were divided into 4 groups of 6 animals and treated as follow: Set 1 included: group 1, control; group 2, the classic kindling PTZ group (UKEOD); group 3, PTZ kindling every other day group with challenge (CKEOD); group 4, PTZ kindling every day group, with challenge (CKED); Set 2 included: group 1, control; group 2, CKEOD group; group 3 and 4, receiving either valproate 200 mg/kg or valproate 300 mg/kg + CKEOD procedure. Results show that CKEOD group significantly reduced the number of injections necessary to reach the fully-kindled state, increased the severity of seizures and improved the stability of seizures. In addition, the CKEOD group significantly increased the level of malondialdehyde and GABA transaminase, reduced the level of reduced glutathione, catalase and GABA. Furthermore, it had no impact on plasma levels of alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT). Valproate 300 mg/kg significantly protected animals against kindling induced by CKEOD. The kindling model with a challenge dose administered on day 1 (CKEOD) thus allows to induce more severe, more stable chronic epilepsy and in a shorter period of time, and could thus contribute to a better understanding of epilepsy, as well as its uses in drug discovery.

Epilepsy is a chronic brain disorder, with anti-epileptic drugs (AEDs) providing relief from hyper-excitability of neurons, but largely failing to restrain neurodegeneration. We investigated a progressive preclinical trial in rats, whereby the test drugs; sodium valproate (SVP; 150 and 300 mg/kg), baclofen (BFN; 5 and 10 mg/kg), and thymoquinone (THQ; 40 and 80 mg/kg) were administered (i.p, once/day for 15 days) alone, and as low dose combinations, and subsequently tested for antiseizure and neuroprotective potential using electrical stimulation of neurons by Maximal electroshock (MES). The seizure stages were monitored, and hippocampal levels of m-TOR, IL-1β, IL-6 were measured. Hippocampal histopathology was also performed. Invitro and Insilco studies were run to counter-confirm the results from rodent studies. We report the synergistic effect of trio-drug combination; SVP (150 mg/kg), BFN (5 mg/kg) and THQ (40 mg/kg) against generalized seizures. The Insilco results revealed that trio-drug combination binds the Akt active site as a supramolecular complex, which could have served as a delivery system that affects the penetration and the binding to the new target. The potential energy of the ternary complex in the Akt active site after dynamics simulation was found to be −370.426 Kcal/mol, while the supramolecular ternary complex alone was −38.732 Kcal/mol, with a potential energy difference of −331.694 Kcal/mol, which favors the supramolecular ternary complex at Akt active site binding. In addition, the said combination increased cell viability by 267% and reduced morphological changes induced by Pentylenetetrazol (PTZ) in HEK-293 cells, which indicates the neuroprotective property of said combination. To conclude, we are the first to report the anti-convulsant and neuroprotective potential of the trio-drug combination.

Background: Enuresis is an uncommon adverse effect of sodium valproate therapy that is unknown to most clinicians. This study provides an overview of the literature on enuresis associated with sodium valproate therapy, discussing the clinical manifestations and possible mechanisms of this side effect. Methods: We reported three cases of enuresis induced by sodium valproate and reviewed the published enuresis cases associated with sodium valproate therapy retrieved from databases. Case presentation and results: Three new patients with epilepsy who presented with enuresis following sodiumvalproate therapy were reported, and 55 published cases of nocturnal enuresis associated with sodium valproate were evaluated. The average age of these patients varied from 4 to 20 years. A total of 48 cases had generalized seizures, seven had focal seizures, and three had unknown seizures. In all the patients, the plasma concentration of sodium valproate was 80.76 ± 14.80µg/mL, within the therapeutic range when enuresis occurred. With discontinuation or reduction of the drug, all the patients recovered completely. Conclusion: Sodium valproate-induced enuresis is a rare and reversible side effect, occurring at a younger age, characterized by the generalized onset of seizures, and a rather high dose. The possible mechanisms include insufficient secretion of anti-diuretic hormones, sleep disorder, and hyperactivity of the parasympathetic system. Clinicians should be aware of this uncommon side effect to avoid an incorrect adjustment of the treatment direction. [ABSTRACT FROM AUTHOR]

Objective:Epilepsy, one of the most common chronic neurological diseases, is characterized by spontaneous recurrent seizures. Many studies, using various experimental epilepsy models, have shown that resveratrol reduces epileptiform activity and has neuroprotective effects. Using an epilepsy model created with penicillin, we aimed to investigate the effect of resveratrol on epileptiform activity in rats.Methods:A total of 40 Wistar albino rats were divided into 5 groups of 8. In the control group, only 2.5 μL of saline was administered intracranially (ic). In the penicillin group, 500 IU of penicillin was given intracranially with no additional procedure. In the resveratrol group, 40 mg/kg of resveratrol was administered intraperitoneally (ip) 20 minutes after penicillin was given intracranially. In the sodium valproate group, 20 minutes after penicillin ic, 300 mg/kg of sodium valproate was administered intraperitoneally. In the resveratrol + sodium valproate group, 20 minutes after penicillin ic, 40 mg/kg of resveratrol was administered intraperitoneally to the right side and 300 mg/kg of sodium valproate ip to the left side. The rats were placed in a stereotaxic device after the procedure and electrocorticogram recordings were captured for 180 minutes.Results:The number of spikes and the average amplitude of the spikes (peak-to-peak) were calculated from the electrophysiological recording data. In the resveratrol group, there was no statistically significant difference in spike frequency and amplitude values. In the resveratrol + sodium valproate group, the spike frequency values decreased significantly from the 30th minutes (P = .028 < .05) and the amplitude decreased significantly from the 60th minutes (P = .018 < .05). Conclusion:In this rat experimental epilepsy model created with penicillin, administration of resveratrol alone did not create a statistically significant difference in epileptiform activity; however, administration of resveratrol with sodium valproate significantly decreased epileptiform activity.

To examine how sodium valproate and carbamazepine improve cognitive function and self-care in Epilepsy Patients (EP). Our facility collected 150 EP patients from September 2020 until June 2022. 70 patients received carbamazepine as the control group, and 80 received it with sodium valproate as the observation group. Both groups recorded EP attack frequency and duration following treatment to compare clinical efficacy. The Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF) were measured before and after treatment, adverse effects were counted, and the patient's ability to perform activities of daily living and activities was assessed by Montreal Cognitive Assessment (MOCA), Activities of Daily Life (ADL), and Barthel Index (BI). The observation group had fewer EP episodes and shorter EP episodes than the control group (P<0.05), and the total effective rate of treatment was greater. After treatment, Nerve Growth Factor and Brain Derived Neurotrophic Factor were higher in the observation group than in the control group (P<0.05). The observation group had fewer adverse effects than the control group (P<0.05). The observation group outperformed the control group in MOCA, ADL, and BI after treatment (P<0.05). Valproate with carbamazepine can reduce EP attacks and improve clinical efficacy and safety. [ABSTRACT FROM AUTHOR]

Introduction: Epileptic neurological disorder, which is controlled with medications such as sodium valproate (one of the treatment priorities for the patients with epilepsy). Polycystic ovary syndrome (PCOS) is one of complication of sodium valproate. Ovulation in PCOs Patients is disrupted, resulting in serious complications, including endometrial hyperplasia with typical and atypical forms, increased the risk of endometrial endometrial cancer, diabetes mellitus, and decreased fertility rates. This study, in accordance with bioinformatics studies and other studies based on the association of miRNA-222 with genes involved in PCOs and hyperandrogenism, was designed to evaluate the association of PCOs in the patients treated with sodium valproate by simultaneously comparing the AMH factor and miRNA-222 marker at specific time periods. Methods: In this case-control study, 33 women with epilepsy before and after use the drug were selected based on inclusion and exclusion criteria. After blood sampling, their plasma was isolated. According to the instructions of the Total RNA extracted kit , cDNA synthesized and miRNA-222 expression was evaluated by RT-qPCR technique and statistical analysis was performed by SPSS 23 software, T-test and ANOVA tests. Results: The results of statistical tests such as T-test and ANOVA test (done with SPSS software) which showed a significant difference (p

Eyelid myoclonus is an idiopathic generalized epileptic syndrome that can occur with or without absence seizures. The features include frequent blinking, an upward roll of the eyeballs, and slight backward movement of the head. It can be spontaneous or stimulated by light. Light and eyelid closure are triggers to the seizures. A 13-year-old young male student presented with a four months history of frequent blinking and abnormal eye movements. There was a positive history of leg tapping while asleep which started a year prior to presentation, but there was no loss of consciousness. On presentation, the patient was a young healthy looking myope who frequently blinks with sudden upward and left jerky movements of the eyeballs. Visual acuity was CF at 2 meters in both eyes improving with -4.50DS to 6/6. Intraocular pressures were 12 mmHg bilaterally. Anterior and posterior segment findings were normal. Brain MRI was normal, but EEG was abnormal with features suggestive of generalized epilepsy. He was co-managed with the neurologist and placed initially on Tabs Sodium valproate 250mg for 3 months. This was modified to Tabs Sodium Valproate (controlled release) 500mg at night since there was little change. This resulted in an appreciable reduction in blinking and abnormal eye movement. The leg tapping stopped on this dose. Eyelid myoclonus (EM) is a rare form of epilepsy. It is of utmost importance to create awareness of the disease among physicians. Early diagnosis and treatment are important prognostic factors of the disease. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To probe into the effects of sodium valproate combined with lamotrigine on cognitive function, immune function and neurological damage of children with epilepsy. METHODS: Retrospective analysis was performed on clinical data of 140 children with epilepsy admitted into the hospital from Jul. 2017 to Jul. 2021, all children were extracted to be divided into the control group (n = 70) and the observation group (n = 70) according to the intervention method. The control group was treated with sodium valproate, while the observation group received lamotrigine on the basis of the control group. Both groups were treated with continuous treatment for 3 months. Before and after treatment, cognitive function [mini-mental state examination (MMSE) score], anxiety [ self-rating anxiety scale (SAS) score], depression [ self-rating depression scale ( SDS) score], immune function [ immunoglobulin G (IgG), immunoglobulin M (IgM)], degree of neurological impairment [clinical neurological impairment rating scale (CSS) score], quality of life [ score of short form for health survey ( SF-36)], and adverse drug reactions in two groups were detected and compared. RESULTS: After treatment, the MMSE scores of two groups were higher than those before treatment, and the SAS and SDS scores were lower than those before treatment; the MMSE scores of the observation group was higher than that of the control group, and the SAS and SDS scores were lower than those of the control group, with statistically significant differences (P<0. 05). After treatment, the levels of IgG and IgM in two groups were lower than those before treatment, and the levels of IgG and IgM in the observation group were lower than those in the control group, with statistically significant differences (P<0. 05). After treatment, the CSS scores of two groups were lower than those before treatment, and the CSS scores of the observation group were lower than those of the control group, with statistically significant differences (P < 0. 05). After treatment, the SF-36 scores of two groups were higher than those before treatment, and the SF-36 scores of the observation group were higher than those of the control group, with statistically significant differences ( P < 0. 05). There was no significant difference in the total incidence of adverse drug reactions between two groups (P>0. 05). CONCLUSIONS: Sodium valproate combined with lamotrigine can effectively improve the cognitive function, anxiety and depression in children with epilepsy, reduce the neurological deficit score, control the recent infection and improve the quality of life in children, and does not increase the obvious adverse drug reactions. [ABSTRACT FROM AUTHOR]

Background: The rational use of medicine is fundamental to ensure effective and safe patient medicine treatment, and hence, should be monitored. Undisputable evidence exists for the teratogenic risk factors associated with sodium valproate. Consequently, the Western Cape Department of Health introduced a policy (2019) recommending alternatives for valproate in women of childbearing age, including lamotrigine or levetiracetam as alternatives for patients on antiretrovirals. This study aimed to describe the change in the consumption of valproate, lamotrigine and levetiracetam after a policy implementation in public sector health facilities of the Western Cape, South Africa. Methods: This observational study followed a quasi-experimental design. Consumption data from the Cape Medical Depot over the period 01 April 2018 to 31 March 2020 were analysed retrospectively. Consumption was presented as a defined daily dose (DDD) per 1000 population per quarter for sodium valproate, levetiracetam and lamotrigine for the Western Cape province, urban and rural areas. Consumption 12 months before was compared with consumption 12 months after policy implementation. Results: Post-policy implementation, valproate consumption remained unchanged provincially (3.3%; p = 0.255), in urban (7.8%; p = 0.255) and rural (1.5%; p = 0.701) areas. Lamotrigine consumption increased significantly provincially (30.7%; p = 0.020) and in urban areas (54.5%; p = 0.002); however, rural (26.1%; p = 0.108) areas did not show significant change. Provincially, valproate consumption remained substantially higher (209 DDDs/1000 population per quarter) compared with lamotrigine consumption (32.22 DDDs/1000 population per quarter). Conclusion: In the Western Cape public sector, the consumption of sodium valproate remained unchanged 12 months after policy implementation. Although there were significant increases in lamotrigine and levetiracetam consumption, the consumption was considerably less compared with sodium valproate consumption. [ABSTRACT FROM AUTHOR]

Background and Objectives: The adverse metabolic effects of long-term antiepileptic drug (AED) therapy are well known. But there is limited data on the same in children from India. This study was designed to look into the effect of long-term AEDs on anthropometry, glycemic parameters, insulin resistance, lipid profile, and hepatic steatosis in a cohort of South Indian children compared to healthy controls. This cross-sectional study was done in a pediatric epilepsy clinic of a tertiary care university teaching hospital. Materials and Methods: Ambulant children aged 5 to 15 years with epilepsy on AEDs for at least one year were identified. This cohort was divided into monotherapy and polytherapy groups. Age- and sex-matched controls were selected from healthy children in the community. All the cases and controls underwent a detailed general physical examination and investigations, including fasting blood glucose, fasting insulin, fasting lipid profile, and liver transaminases along with ultrasonogram of abdomen. Statistical Analysis Used: Student's t-test, chi-square test, ANOVA/Kruskall--Walli test with Bonferroni adjustment. Results: Fifty children on long-term AED therapy (25 on monotherapy and 25 on polytherapy) and 22 controls were included in the study. Children on AED had significantly higher LDL-cholesterol, fasting blood glucose, and insulin resistance compared to controls. Four children on multiple AEDs had non-alcoholic fatty liver disease (NAFLD). Children taking oxcarbazepine regimen were found to have an adverse metabolic profile compared to those on other drugs. Conclusion: This cohort of South Indian children with epilepsy on long-term AED therapy had an adverse metabolic profile compared to matched healthy controls. Further larger community-based studies are needed to further characterize the association and develop successful intervention strategies. Emphasis on a healthy life style should be part of comprehensive epilepsy care program. [ABSTRACT FROM AUTHOR]

Objective: To assess vitamin D status of children on long-term anticonvulsants, including the less studied widely used levetiracetam, and the potential risk factors for deficiency. Method: Children on antiepileptic drugs (cases, n = 269) were compared with controls (n = 295) for serum biochemistry, 25OHD, parathormone (PTH), sun exposure, dietary calcium, and vitamin D intake. Results: Cases had lower serum 25OHD [median (IQR) 18.4 (11.5–24.1) ng/mL] compared to controls [20.8 (15.4–26.2] ng/mL, p < 0.001), as well as more frequent vitamin D deficiency (25OHD < 12 ng/mL, 27.1%) and insufficiency (25OHD < 20 ng/mL, 57.6%) than did controls (11.2% and 46.1%, respectively). Significantly lower median (IQR) serum calcium [8.8 (8.1–9.4) vs. 9.2 (8.5–10.0) mg/dL], phosphorous [3.8 (3.3–4.2) vs. 4.7 (4.0–5.3) mg/dL), and higher PTH [58.4 (42.9–85.8) vs. 38.9 (24.6–55.5) pg/mL, p < 0.001 for all] and proportion of elevated alkaline phosphatase (11.2% vs. 5.1%, p < 0.01) was seen in cases versus controls. Vitamin D deficiency was present in 53.4% of children with cerebral palsy (CP) versus 19.9% in those without CP (p < 0.001). Serum 25OHD did not differ between patients on cytochrome P450 inducers versus noninducers, neither among the 3 major groups, users of carbamazepine, valproate, and levetiracetam. Logistic regression analysis showed serum 25OHD < 12 ng/mL to be independently influenced by case or control status, presence of CP, and season of sampling. Conclusion: Vitamin D deficiency is common with anticonvulsant therapy, especially in those having CP. In Kerala, the hot, dry season from March to May is protective. [ABSTRACT FROM AUTHOR]

Background: L-carnitine, as an endogenous compound, has paradoxical effects on seizures. This study aimed to evaluate the effect of acute administration of L-carnitine alone or combination with sodium valproate on pentylenetetrazole (PTZ) induced myoclonic and tonic seizure thresholds in mice. Materials and Methods: In this study, 64 male NMRI mice (25-30 g) were divided into 8 groups (8 animals in each group). Normal saline (as solvent), L-carnitine (50, 100, 150 and 200 mg/kg), sodium valproate (50 and 150 mg/kg) and combination of the ineffective doses of L-carnitine/sodium valproate (100.50 mg/kg) were administered by gavage. L-carnitine and sodium valproate were administrated 4 and 2 hours before seizure induction, respectively. Intravenous infusion of PTZ was used to induce seizure induction. All data were analyzed using a one-way analysis of variance (ANOVA) via SPSS version 21.0 software. Results: The results showed that L-carnitine at doses of 150 and 200 mg/kg significantly increased the threshold of myoclonic and tonic seizures compared to the control group (P

Background: Among antiepileptic drugs (AEDs), sodium valproate alone or in the combination of topiramate (TPM) for treating refractory epilepsy was controversial. This meta-analysis aimed to systematically evaluate the clinical effects of these two regimens in this population.Methods: Relevant studies up to August 2021 were identified through systematic searches of CNKI, Wanfang, PubMed, and Embase databases. We assessed the effectiveness and the frequency of absence seizures, atonic seizures, and tonic–clonic seizures. The included literature's risk of bias was evaluated using the Cochrane Collaboration's Risk of Bias tool. Sensitivity analysis was conducted to confirm the results' stability. STATA 15.0 was utilized for all pooled analyses in the included studies.Results: Totally 10 articles were determined for our meta-analysis, involving 976 patients with epilepsy in total (combined group, n = 488; monotherapy group, n = 488). The results of this meta-analysis indicated that the total effective rate of sodium valproate combined with TPM was higher than that of sodium valproate alone (random-effect model: OR = 3.52; 95% CI 1.47 to 8.47; p < 0.001; I2 = 73.8%). The frequency of absence seizures in the combined group was lower (fixed-effect model: WMD = −6.02; 95% CI −6.50 to −5.54; I2 = 0.0%) than that in the monotherapy group, with a statistical difference (p < 0.05). The combined group had lower frequency of atonic seizures (WMD = −4.56, 95% CI −6.02 to −3.10; I2 = 82.6%) and lower frequency of tonic–clonic seizures (WMD = −3.32; 95% CI −4.75 to −1.89; I2 = 96.4%). In addition, the distinct difference of adverse events was non-existent between two groups.Conclusions: Sodium valproate combined with TPM was more effective than sodium valproate alone for epilepsy therapy. This meta-analysis provides feasibility data for a larger-scale study on AED therapy of refractory epilepsy and may contribute to better therapy strategies for epilepsy clinically.

Background: Among antiepileptic drugs (AEDs), sodium valproate alone or in the combination of topiramate (TPM) for treating refractory epilepsy was controversial. This meta-analysis aimed to systematically evaluate the clinical effects of these two regimens in this population. Methods: Relevant studies up to August 2021 were identified through systematic searches of CNKI, Wanfang, PubMed, and Embase databases. We assessed the effectiveness and the frequency of absence seizures, atonic seizures, and tonic–clonic seizures. The included literature's risk of bias was evaluated using the Cochrane Collaboration's Risk of Bias tool. Sensitivity analysis was conducted to confirm the results' stability. STATA 15.0 was utilized for all pooled analyses in the included studies. Results: Totally 10 articles were determined for our meta-analysis, involving 976 patients with epilepsy in total (combined group, n = 488; monotherapy group, n = 488). The results of this meta-analysis indicated that the total effective rate of sodium valproate combined with TPM was higher than that of sodium valproate alone (random-effect model: OR = 3.52; 95% CI 1.47 to 8.47; p < 0.001; I 2 = 73.8%). The frequency of absence seizures in the combined group was lower (fixed-effect model: WMD = −6.02; 95% CI −6.50 to −5.54; I 2 = 0.0%) than that in the monotherapy group, with a statistical difference (p < 0.05). The combined group had lower frequency of atonic seizures (WMD = −4.56, 95% CI −6.02 to −3.10; I 2 = 82.6%) and lower frequency of tonic–clonic seizures (WMD = −3.32; 95% CI −4.75 to −1.89; I 2 = 96.4%). In addition, the distinct difference of adverse events was non-existent between two groups. Conclusions: Sodium valproate combined with TPM was more effective than sodium valproate alone for epilepsy therapy. This meta-analysis provides feasibility data for a larger-scale study on AED therapy of refractory epilepsy and may contribute to better therapy strategies for epilepsy clinically. [ABSTRACT FROM AUTHOR]

Objectives Epilepsy is a relatively common disease in childhood. In some patients, the electroencephalogram (EEG) is abnormal despite the clinical control of seizures. Studies have identified the adverse effects of epileptic discharges on cognition, learning, behavior, and seizure recurrence in children. This study investigated the Levetiracetam effect on epileptic discharges in the interictal phase of EEG in epileptic children. Materials & Methods This clinical trial was conducted on 54 epileptic children aged 2 to 15 years, whose clinical seizures were controlled by sodium valproate in the last six months but still had epileptic discharges in EEG. The participants were divided into two groups: an intervention group (21 people), for which Levetiracetam was added to sodium valproate, and a control group (33 people), for which treatment with sodium valproate alone was continued. The patients were then followed for one year. Results The percent normalization of epileptic discharges in the intervention and control groups was 66.7% and 57.1% (P = 0.500), respectively. Also, the mean time for the normalization of epileptic discharges in the intervention and control groups was 12.60±8.25 and 20.57±12.67 months (P = 0.042), respectively. Conclusion In children with controlled seizures whose EEG was still abnormal, sodium valproate therapy alone and combined with Levetiracetam effectively reduced the severity of epileptic discharges. However, the addition of Levetiracetam to sodium valproate normalized EEG more rapidly. [ABSTRACT FROM AUTHOR]

Introduction: Consuming antidepressant medications induce several problems leading to the need for alternative agents for emotional disturbances. Antidepressant medications increase the seizure risk; thus, alternative treatments, like Antiepileptic Drugs (AED), might be useful for patients with epilepsy comorbid with a psychiatric disorder. The present study evaluated the behavioral effects of sodium valproate, a none effective dose in seizure treatment [100 mg/kg; Intraperitoneal (IP)] along with the application of Low-Frequency Stimulations (LFS) during CA1 hippocampal kindling. Methods: In total, 42 male rats were randomly divided into 6 groups, including control group with intact animals handled daily (I); sham group which was subjected to the surgical process, but received no real stimulation (II); saline-kindled Kindled group (S.kindled) which were stimulated daily with the following protocol: 3 strain of 50Hz monophasic pulses of 1ms duration applied 12 times a day with the threshold intensity at intervals of 10 minutes where saline was administrated 15 min before kindling stimulations (III); saline-kindled-LFS group (K4LFS) in which saline was injected 15 min before kindling stimulations and LFS was applied daily after the termination of kindling stimulation (IV ); drug-kindle group (Drug100.kindled) that underwent rapid kindling procedure daily where sodium valproate (100 mg/kg) was administrated 15 min before kindling stimulations(V), and drug-kindled-LFS (Drug100.kindled.4LFS) group in which drug and LFS were administrated respectively before and after kindling stimulations (VI). The behavioral tests were assessed using elevated plus maze, open field, and forced swim tests. Results: The combination of sodium valproate (100 mg/kg) and LFS significantly decreased cumulative seizure severity compared with the kindle group. Thus, it provided a strong seizure suppressing effect. Additionally, sodium valproate and LFS increased the percentage of Open Arms (OAs) entries and the OAs exploration; they also decreased jumping from elevated plus maze test and rearing in open field test. Furthermore, there was no significant change in the OAs entries and OAs exploration percentages, jumping from apparatus, and rearing in open field in Drug100. Kindled, K4LFS, and Drug100.kindled.LFS groups, compared with the sham group. There was no significant difference in the latency to first immobility and the duration of immobility in K4LFS groups compared with the S. kindled group. In the drug-kindled group, the latency to first immobility significantly increased, and the duration of immobility decreased, compared with the S. kindled group. Besides, the latency to first immobility significantly increased, and the duration of immobility decreased in drug-kindled-LFS, compared to S. kindled group; however, the latency to first immobility was not significantly changed, compared to drug-kindled groups. Conclusion: Sodium valproate and LFS can modulate the function of the brain regions involved in emotional processing in epilepsy, as well as anxiety- and depressive-like behaviors. Such a combination could also decrease emotional disturbances induced by the kindling process.

We conducted this meta-analysis to assess the effects of sodium valproate (VPA) monotherapy on blood liver enzymes in patients with epilepsy. PubMed, Web of Science, EBSCO, Cochrane Library, Wanfang, China national knowledge infrastructure databases were searched. Nine studies were included. Results showed: (1) The overall SMD for blood AST, ALT, and GGT levels of VPA monotherapy group versus control group were 0.70 (95% CI=0.31 to 1.09, Z=3.52, p=0.0004), 0.47 (95% CI=− 0.01 to 0.95, Z=1.91, p=0.06), 0.44 (95% CI=0.29 to 0.60, Z=5.55, p<0.00001), respectively. (2) In subgroup meta-analysis, increased blood AST and GGT levels were observed in epileptic minors (AST: total SMD=0.85, 95% CI=0.40 to 1.30, Z=3.69, p=0.0002; GGT: total SMD=0.46, 95% CI=0.29 to 0.63, Z=5.25, p<0.00001). Elevated blood ALT level was observed in Asian patients receiving VPA monotherapy (total SMD=0.70, 95% CI=0.51 to 0.90, Z=7.01, p<0.00001), and the early stage of VPA monotherapy (total SMD=0.93, 95% CI=0.57 to 1.29, Z=5.09, p<0.00001). Overall, our results indicated that blood AST and GGT were significantly increased in epileptic minors receiving VPA monotherapy. The elevation of blood ALT was observed in Asian patients and the early stage of VPA monotherapy. However, due to the small number of included studies, our results should be considered with caution. [ABSTRACT FROM AUTHOR]

This study aimed to assess the national trends in anti-seizure medication (ASM) prescription in Chinese adult outpatients with epilepsy over a 6-year period from 2013 to 2018. Prescriptions for adult outpatients with epilepsy from hospitals in six major cities were extracted from the database of the Hospital Prescription Analysis Cooperative Project. Trends in the annual prescriptions and expenditure of ASM were analyzed. Prescription patterns (monotherapy or combination therapy) were also assessed. A total of 225,767 prescriptions from 60 hospitals were eligible and extracted for analysis. The number of ASM prescriptions increased from 28,360 in 2013 to 44,110 in 2018, and the corresponding cost increased from 9,452,990 Chinese Yuan (CNY) in 2013 to 14,627,865 CNY in 2018. The share of newer ASM use increased continuously, accounting for 56.75% of prescriptions and 85.03% of expenditure in 2018. The most frequently prescribed ASMs were sodium valproate and levetiracetam. The proportion of sodium valproate use decreased, while the proportion of levetiracetam use increased dramatically in terms of both ASM prescriptions and expenditure. Monotherapy was more frequent than combination therapy. The three most common combination therapies were sodium valproate/lamotrigine, levetiracetam/oxcarbazepine, and sodium valproate/levetiracetam. In summary, ASM use increased rapidly in terms of the number of ASM prescriptions and cost during the 6-year period, which raises concern regarding the rational use and pharma-economic profiles of ASMs. In place of valproate, levetiracetam became the most frequently used ASM. The development of ASM prescription is in line with therapy guidelines and reflects the current state of research in China.