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Background Sodium valproate (VPA) has been associated with a reduced risk of head and neck cancer development. The potential protective mechanism of action is believed to be via inhibition of histone deacetylase and subsequent epigenetic reprogramming. SAVER is a phase IIb open-label, randomised control trial of VPA as a chemopreventive agent in patients with high-risk oral epithelial dysplasia (OED). The aim of the trial is to gather preliminary evidence of the clinical and biological effects of VPA upon OED and assess the feasibility and acceptability of such a trial, with a view to inform a future definitive phase III study. Methods One hundred and ten patients with high-risk OED will be recruited from up to 10 secondary care sites in the UK and randomised into either VPA or observation only for 4 months. Women of childbearing potential will be excluded due to the teratogenic properties of VPA. Tissue and blood samples will be collected prior to randomisation and on the last day of the intervention/observation-only period (end of 4 months). Clinical measurement and additional safety bloods will be taken at multiple time points during the trial. The primary outcome will be a composite, surrogate endpoint of change in lesion size, change in grade of dysplasia and change in LOH profile at 8 key microsatellite regions. Feasibility outcomes will include recruitment targets, compliance with the study protocol and adverse effects. A qualitative sub-study will explore patient experience and perception of the trial. Discussion The current management options for patients with high-risk OED are limited and mostly include surgical resection and clinical surveillance. However, there remains little evidence whether surgery can effectively lead to a notable reduction in the risk of oral cancer development. Similarly, surveillance is associated with concerns regarding delayed diagnosis of OED progressing to malignancy. The SAVER trial provides an opportunity to investigate the effects of a repurposed, inexpensive and well-tolerated medication as a potential chemopreventive strategy for patients with high-risk OED. The clinical and biological findings of SAVER will inform the appropriateness, design and feasibility of a definitive phase III trial. Trial registration The trial is registered with the European Clinical Trials Database (Eudra-CT 2018-000197-30). (http://www.isrctn.com/ISRCTN12448611). The trial was prospectively registered on 24/04/2018.

Background/aim Sleep-deprivation disrupts prepulse inhibition of acoustic startle reflex and can be used to mimic psychosis in experimental animals. On the other hand, it is also a model for other disorders of sensory processing including migraine. The aim of this study is to assess the effects of sodium valproate, a drug that is used in a variety of neuropsychiatric disorders, on normal and disrupted sensorimotor gating in rats. Materials and methods 62 Wistar Albino rats were randomly distributed into 8 groups. Subchronic and intraperitoneal sodium valproate were administrated to the sleep-deprived and non-sleep-deprived rats by either in 50-100 or 200 mg/kg/day. Prepulse inhibition test and locomotor activity test were performed. Sleep-deprivation induced by the modified multiple platform method. Results Sleep-deprivation impaired prepulse inhibition, decreased startle amplitude and increased locomotor activity. Sodium valproate did not significantly alter prepulse inhibition and locomotor activity in non-sleep-deprived and sleep-deprived groups. On the other hand, all doses decreased locomotor activity in drug treated groups, and low dose improved sensorimotor gating and startle amplitude after sleep-deprivation. Conclusion Low dose sodium valproate improves sleep-deprivation-disrupted sensorimotor gating, and this finding may rationalize the use of sodium valproate in psychotic states and other disorders of sensory processing. Dose-dependent effects of sodium valproate on sensorimotor gating should be investigated in detail.

BACKGROUND Sodium valproate is widely used in the treatment of epilepsy in clinical practice. Most adverse reactions to sodium valproate are mild and reversible, while serious idiosyncratic side effects are becoming apparent, particularly hepatotoxicity. Herein, we report a case of fatal acute liver failure (ALF) with thrombotic microangiopathy (TMA) caused by treatment with sodium valproate in a patient following surgery for meningioma. CASE SUMMARY A 42-year-old man who received antiepileptic treatment with sodium valproate after surgery for meningioma exhibited extreme fatigue, severe jaundice accompanied by oliguria, soy sauce-colored urine, and ecchymosis. His postoperative laboratory values indicated a rapid decreased platelet count and hemoglobin level, severe liver and kidney dysfunction, and disturbance of the coagulation system. He was diagnosed with drug-induced liver failure combined with TMA. After plasma exchange combined with hemoperfusion, pulse therapy with high-dose methylprednisolone, and blood transfusion, his liver function deteriorated, and finally, he died. CONCLUSION ALF with TMA is a rare and fatal adverse reaction of sodium valproate which needs to be highly valued.

Aim: The aim was to evaluate the “effect size (ES),” tolerability, and acceptability of lithium, carbamazepine, and sodium valproate in the acute phase treatment of pediatric Bipolar 1 disorder patients during manic phase. Materials and Methods: This hospital-based, prospective, open-label study included 67 patients in manic phase of bipolar I disorder, aged 6–17 years, after informed consent by the caregivers. The patients were randomly assigned to the lithium group (n = 30), carbamazepine group (n = 20), and sodium valproate group (n = 17). They were assessed with the Schedule for Affective Disorders for School Age Children's-Present and Life time version administered to the parent and child separately, Conner's Abbreviated Rating Scale, and Cassidy Scale for Manic States (CSMS). Lithium was started in the dose of 30 mg per kg of body weight, carbamazepine in the dose of 10–20 mg/kg/day, and sodium valproate in the dose of 10–20 mg/kg body weight. Antipsychotic (chlorpromazine [CPZ] 100–500 mg per day or haloperidol up to 750 mg of CPZ equivalent) was allowed in the study. Injection haloperidol 10 mg and injection promethazine 50 mg intramuscular were allowed for initial 3–5 days to combat acute agitation. Rescue medication such as injection lorazepam 2–4 mg intramuscular was allowed throughout the study duration. The patients were rated weekly on CSMS, Bipolar Clinical Global Impression, Udvalg for kliniske Undersogelser Side Effect Rating Scale, and side effect checklist for lithium, sodium valproate, and carbamazepine, respectively. The serum level of concerned drug was obtained at weekly intervals and dose hiked, if needed to get target serum level. Results: The response rate was 90% in lithium group, 70% in carbamazepine group, and 88% in sodium valproate group on the basis of ≥33% reduction from baseline CSMS. The effects of change of CSMS over the 6 weeks across the three treatment group were found to be highly statistically significant. Conclusions: In the acute phase treatment of pediatric bipolar 1 disorder patients during manic phase, the ES for lithium was 0.85, for carbamazepine 0.71, and for sodium valproate 0.84. These agents are well tolerated in treating bipolar disorder in children.

Aim: This study examines the effect of alpha-lipoic acid (ALA) on sodium valproate-induced liver injury through histological features of mice liver tissue. Materials and Methods: Mice were divided into three groups; (1) vehicle group, (2) sodium valproate group, and (3) sodium valproate-ALA group. The vehicle group was injected with saline intraperitoneal (i.p.) for 28 days. The sodium valproate group was injected with sodium valproate 300 mg/kg, i.p. daily for 2 weeks, after which the vehicle was administered daily until day 28. The sodium valproate-ALA group was injected with sodium valproate 300 mg/kg daily for 2 weeks before the administration of ALA 100 mg/kg i.p. until day 28. The mice were euthanized, and the liver was extracted for histopathological examination. Results: Histopathological examination of the liver section of the vehicle group showed a normal structure of the liver. Two weeks after the administration of sodium valproate, histopathological examination showed an abnormal structure of the liver, with necrotic appearance and inflammatory cells. Moreover, treatment with ALA after the administration of sodium valproate notably ameliorated hepatic histopathological lesions and the liver structure corresponded to a normal liver structure. Conclusion: ALA ameliorates sodium valproate-induced liver injury in mice.

Background and Aims: Anticonvulsants are used routinely for seizure prophylaxis in patients with supratentorial tumour who present with/without seizures. Excessive use of prophylactic anticonvulsant may delay the recovery from anaesthesia. We have studied the recovery profiles of patients who received an additional dose of anticonvulsant in comparison with those who received only the regular dose. Methods: In this prospective observational study, patients were anaesthetised using standard anaesthesia protocol. An additional dose of anticonvulsant was administered in one group, while the other group received only the regular dose. Time taken for extubation, eye opening, obeying commands and orientation were compared between the two groups. Haemodynamics, depth of anaesthesia, the plasma anticonvulsant levels and the incidence of seizures were compared between the two groups. Results: A total of 36 patients were studied, of which 19 received regular dose and 17 received an additional dose. There was no significant difference in recovery time between the two groups. Subgroup analysis was performed for phenytoin and sodium valproate. There was a clinically significant delay in recovery in patients who received an additional phenytoin compared to those who received regular dose (time to obey commands >15 min and orientation time >1hour) but, it was not statistically significant. Administration of an additional dose of valproate did not prolong the recovery time. Conclusion: An additional dose of sodium valproate did not cause a delay in recovery both, clinically and statistically. However, the administration of an additional dose of phenytoin caused a clinically significant delay in recovery but was not statistically significant.

Objective: Current methods for the diagnosis of ventriculoperitoneal (VP) shunt malfunction lack specific standards; therefore, it may be missed or misdiagnosed. Hence, providing a reliable diagnostic method will help improve the accuracy of preoperative decision-making. Therefore, the aim of the study was to provide a new method for the diagnosis of VP shunt malfunction. Methods: After in vitro testing, we enrolled a total of 12 patients with VP shunt malfunction. Before revision surgery, 0.1 mL of a 5% sodium valproate (SV) solution was injected into the reservoir; 0.1 mL of the cerebrospinal fluid (CSF) was withdrawn 20 minutes later from the reservoir to measure the SV concentration. The process was repeated on the seventh day after surgery and compared with the preoperative results. Results: The mean ± standard deviation preoperative SV concentration in the cerebrospinal fluid was greater than the postoperative concentration (5967.8 ± 1281.3 vs 391.1 ± 184.6 μg/mL, P = .001). Conclusion: The proposed method is a reliable, safe, and relatively simple alternative for the diagnosis of VP shunt malfunction and further provides a reference for treatment.

Efficacy of levetiracetam (LEV) combined with sodium valproate (SV) on pediatric epilepsy and its effect on serum miR-106b in children were investigated. One hundred and twenty children with epilepsy in Xuzhou Children's Hospital from July 2015 to July 2017 were enrolled, and divided into control group (n=60) and observation group (n=60) according to random sampling. Additionally, 100 children undergoing normal physical examination were collected as normal group. Patients in the control group were treated with SV, and patients in the observation group were treated with SV and LEV. RT-qPCR was used for detecting the relative expression of serum miR-106b in children. The clinical efficacy was evaluated. After treatment, the relative expression of serum miR-106b in the control group was significantly higher than that in the observation group (P

Background A pattern of major and minor congenital anomalies, facial dysmorphic features, and neurodevelopmental difficulties, including cognitive and social impairments has been reported in some children exposed to sodium valproate (VPA) during pregnancy. Recognition of the increased risks of in utero exposure to VPA for congenital malformations, and for the neurodevelopmental effects in particular, has taken many years but these are now acknowledged following the publication of the outcomes of several prospective studies and registries. As with other teratogens, exposure to VPA can have variable effects, ranging from a characteristic pattern of major malformations and significant intellectual disability to the other end of the continuum, characterised by facial dysmorphism which is often difficult to discern and a more moderate effect on neurodevelopment and general health. It has become clear that some individuals with FVSD have complex needs requiring multidisciplinary care but information regarding management is currently lacking in the medical literature. Methods An expert group was convened by ERN-ITHACA, the European Reference Network for Congenital Malformations and Intellectual Disability comprised of professionals involved in the care of individuals with FVSD and with patient representation. Review of published and unpublished literature concerning management of FVSD was undertaken and the level of evidence from these sources graded. Management recommendations were made based on strength of evidence and consensus expert opinion, in the setting of an expert consensus meeting. These were then refined using an iterative process and wider consultation. Results Whilst there was strong evidence regarding the increase in risk for major congenital malformations and neurodevelopmental difficulties there was a lack of high level evidence in other areas and in particular in terms of optimal clinical management.. The expert consensus approach facilitated the formulation of management recommendations, based on literature evidence and best practice. The outcome of the review and group discussions leads us to propose the term Fetal Valproate Spectrum Disorder (FVSD) as we feel this better encompasses the broad range of effects seen following VPA exposure in utero. Conclusion The expert consensus approach can be used to define the best available clinical guidance for the diagnosis and management of rare disorders such as FVSD. FVSD can have medical, developmental and neuropsychological impacts with life-long consequences and affected individuals benefit from the input of a number of different health professionals. Electronic supplementary material The online version of this article (10.1186/s13023-019-1064-y) contains supplementary material, which is available to authorized users.

Schizophrenia patients have significantly lower life expectancy than the general population. Clozapine is the most effective antipsychotic to reduce the mortality rate in these patients. Here, we report a schizophrenic patient with clozapine‐induced myocarditis and successful retrial. In the first trial, clozapine was discontinued due to myocarditis. In the second trial, the titration rate was slower, and sodium valproate was not coadministered with clozapine. The patient has not developed myocarditis over 3.5 years of observation. It may be possible to take clozapine for a long time even after clozapine‐induced myocarditis, and thus improve the life expectancy of schizophrenia patients.

Status epilepticus has been shown to activate the proliferation of neural stem cells in the hippocampus of the brain, while also causing a large amount of neuronal death, especially in the subgranular zone of the dentate gyrus and the subventricular zone. Simultaneously, proliferating stem cells tend to migrate to areas with obvious damage. Our previous studies have clearly confirmed the effect of sodium valproate on cognitive function in rats with convulsive status epilepticus. However, whether neurogenesis can play a role in the antiepileptic effect of sodium valproate remains unknown. A model of convulsive status epilepticus was established in Wistar rats by intraperitoneal injection of 3 mEq/kg lithium chloride, and intraperitoneal injection of pilocarpine 40 mg/kg after 18-20 hours. Sodium valproate (100, 200, 300, 400, 500, or 600 mg/kg) was intragastrically administered six times every day (4-hour intervals) for 5 days. To determine the best dosage, sodium valproate concentration was measured from the plasma. The effective concentration of sodium valproate in the plasma of the rats that received the 300-mg/kg intervention was 82.26 ± 11.23 μg/mL. Thus, 300 mg/kg was subsequently used as the intervention concentration of sodium valproate. The following changes were seen: Recording excitatory postsynaptic potentials in the CA1 region revealed high-frequency stimulation-induced long-term potentiation. Immunohistochemical staining for BrdU-positive cells in the brain revealed that sodium valproate intervention markedly increased the success rate and the duration of induced long-term potentiation in rats with convulsive status epilepticus. The intervention also reduced the number of newborn neurons in the subgranular area of the hippocampus and subventricular zone and inhibited the migration of newborn neurons to the dentate gyrus. These results indicate that sodium valproate can effectively inhibit the abnormal proliferation and migration of neural stem cells and newborn neurons after convulsive status epilepticus, and improve learning and memory ability.

Valproic acid is a commonly prescribed drug used in various conditions including seizures, bipolar disorder, mood disorder, and migraine headaches. Confusion and lethargy among patients on valproic acid need urgent attention as it can cause increased levels of ammonia, which can lead to the development of cerebral edema and even cerebral herniation in severe cases. Here, we describe a case of hyperammonemic coma induced by valproic acid toxicity. The condition was rapidly resolved using dual therapy involving extracorporeal removal and levocarnitine.

Background Migraine is a painful and disabling nervous disorder which negatively affects the quality of life. Migraineurs may suffer from a generalized vasomotor dysfunction. Statins improve vasomotor and vascular function, with their pleiotropic effects. We aimed to assess efficacy and safety of adding Atorvastatin to prophylactic regimen in better control of migraine with aura. Methods This triple-blind controlled clinical trial was on 68 patients with migraine with aura. An interval of at least 1 month was given to evaluate vitamin D3 level and eligibility. In patients with vitamin D3 deficiency, the correction with vitamin D supplementation was provided. The patients were randomly assigned to receive atorvastatin 20 mg plus sodium valproate 500 mg or placebo plus sodium valproate 500 mg once a day for 2 months. The patients were evaluated based for the number of attacks and pain severity based on Visual Analogue Scale. Results There was a significant (p = 0.0001) improvement in severity of pain and number of migraine attacks by adding Atorvastin to the prophylactic regimen of patients with migraine with aura. After controlling for variable parameters, the differences between two arms of the study was yet statistically significant (p = 0.0001). A significant number of participants in intervention group were satisfied by their treatment (p = 0.001) with no remarkable side effects (P = 0.315). Conclusions Adding atorvastatin to migraine with aura preventive regimen may help reduce the number of acute attacks and pain severity without causing considerable side effects and led to a better patient satisfaction. Trial registration IRCT20180106038242N1. Registered: 7 February 2018.

Stevens-Johnson syndrome is a severe immune-mediated cutaneous reaction occurring due to exposure to certain drugs. Lamotrigine is an FDA approved drug used in the treatment of bipolar depression. When it is given concomitantly with sodium valproate, the risk of developing Stevens-Johnson syndrome increases. Here we present the report of a patient with bipolar depression who developed serious skin rashes while on lamotrigine and NSAID prescribed by a local doctor, who recovered after timely management. This case highlights the importance of following proper dosing, drug escalation regimen and managing drug interactions during lamotrigine therapy.

Alternative therapies are necessary to treat catatonia in patients with comorbidities that are not amenable to therapy with benzodiazepines or ECT. This is a patient with schizophrenia with catatonic features and a history of polysubstance abuse. Consequently, he was not a candidate for treatment with benzodiazepines, so an alternative needed to be found. GABAergic medications have been used previously as alternatives to benzodiazepines and ECT. In this case we chose sodium valproate, due to its cross-reaction with GABAergic systems. There are five reported cases using sodium valproate. Three of which were treated with intravenous valproate, while the remaining two do not specify the route of administration. We present a case where oral sodium valproate was used successfully for both acute and long-term catatonic treatment. To our knowledge, no other report has looked at both acute and long-term treatment with sodium valproate. Oral sodium valproate can be considered for patients with substance use disorders like COPD, sleep apnea or myasthenia gravis in which benzodiazepines are contraindicated and where ECT is not an option for treatment.

Background: We aimed to investigate the therapeutic effect of sodium valproate combined with levetiracetam on pediatric epilepsy and the effects of nerve growth factor and γ-aminobutyric acid. Methods: Eighty-three epileptic children admitted to Xuzhou Municipal Hospital of Xuzhou Medical University (Xuzhou, China) from Jan 2018 to Nov 2019 were collected and divided into a control group (40 cases, treated with sodium valproate alone) and an observation group (43 cases, treated with sodium valproate combined with levetiracetam). The therapeutic effect and incidence of adverse reactions were observed. The levels of nerve growth factor (NGF), γ-aminobutyric acid (GABA) and serum neuron-specific enolase (NSE) of children were compared. Changes of cognitive function and the total effective rate were evaluated. Logistic regression analysis was used to analyze the risk factors affecting the therapeutic effect. Results: After treatment, NGF, GABA and NSE in the observation group were significantly improved compared with those before treatment. The cognitive function of the observation group was significantly improved after treatment when compared with the control group. The total effective rate in the observation group was higher than that in the control group. Adverse reactions in the observation group were less than those in the control group. Seizure type, NGF, GABA, NSE and treatment methods were independent risk factors affecting the therapeutic effect of pediatric epilepsy. Conclusion: The application of sodium valproate combined with levetiracetam in the treatment of pediatric epilepsy is helpful to improve the overall therapeutic effect, significantly improve the cognitive function of children, and improve the levels of NGF, GABA and NSE.

ObjectiveThis study aimed to assess the efficacy of concurrent magnesium-sodium valproate therapy and compare it with either magnesium or sodium valproate alone in migraine prophylaxis.Materials and methodsThis randomized single-center double-blind parallel-group controlled clinical trial study was conducted on migraine patients within the age range of 18–65 years. The subjects with at least four monthly attacks were randomly assigned to group A (n = 82) sodium valproate, group B (n = 70) magnesium with sodium valproate, and group C (n = 70) magnesium. The patients passed a one-month baseline without prophylactic therapy and then received a 3-month treatment. The characteristics of migraine, including frequency, severity, duration of the attacks, and the number of painkillers taken per month, were monthly recorded in each visit. The Migraine Disability Assessment (MIDAS) and Headache Impact Test-6 (HIT-6) scores were recorded at the baseline and after 3 months of treatment in each group. Within- and between-group analyses were performed in this study.ResultsThe obtained results revealed a significant reduction in all migraine characteristics in all groups compared to those reported for the baseline (P P = 0.525); nevertheless, three other parameters showed a significant reduction in group B, compared to those reported for group A in the third month (P P P P ConclusionThe obtained results of this study revealed that magnesium could enhance the antimigraine properties of sodium valproate in combination therapy and reduce the required valproate dose for migraine prophylaxis.

Pediatric epilepsy comprises chronic neurological disorders characterized by recurrent seizures. Sodium valproate is one of the common antiseizure medications used for treatment. Glucuronide conjugation is the major metabolic pathway of sodium valproate, carried out by the enzyme uridine 5′-diphosphate (UDP) glucuronosyl transferase (UGT) whose gene polymorphisms may alter the clinical outcome. The objective of this study was to assess the association between UGT1A6 genetic polymorphism and clinical outcome in terms of efficacy and tolerability in pediatric epileptic patients on sodium valproate monotherapy. Pediatric epileptic patients (n=65) aged 2-18 years receiving sodium valproate monotherapy for the past one month were included. Genetic polymorphism patterns of UGT1A6 (T19G, A541G, A552C) were evaluated by PCR-RFLP. Clinical outcome was seizure control during the 6 months observation period. Tolerability was measured by estimating the hepatic, renal, and other lab parameters. Out of 65 patients, TT (40%), TG (57%), and GG (3%) patterns were observed in UGT1A6 (T19G) gene, AA (51%), AG (40%), and GG (9%) in (A541G) gene, and AA (43%), AC (43%), and CC (14%) in (A552C) gene. No statistical difference in clinical outcome was found for different UGT1A6 genetic polymorphism patterns. We concluded that different patterns of UGT1A6 genetic polymorphism were not associated with the clinical outcome of sodium valproate in terms of efficacy and tolerability. Sodium valproate was well-tolerated among pediatric patients with epilepsy and can be used as an effective antiseizure medication.

The antiepileptic Valproic acid (VPA) changes the oxidative/ anti-oxidative balance that results in oxidative stress and maybe an increased risk of cardiac dysfunction. The aim of this study was to investigate the effect of VPA on ventricular function in epileptic children. We designed a study to evaluate ventricular function in epileptic children who had received VPA for at least one year. All subjects were evaluated using standard echocardiography, pulsed wave Doppler (PWD), and tissue Doppler imaging (TDI). This study consisted of 60 patients with epilepsy (mean age 10.30±3.21 years) and 60 healthy subjects in the control group (mean age 10.28±3.18 years). The duration of antiepilepsy medication ranged from 1.4 to 10 years, and the dose of VPA was 5-30 mg/kg. The ejection fraction and fractional shortening (P=0.841 and 0.064, respectively) were not significantly different between the two groups. The present study reports subclinical right and left ventricular systolic and diastolic dysfunction along with longitudinal ventricular motion disorder. It is recommended the evaluation of subclinical cardiac dysfunction in children treated by VPA.

Efficacy and safety of sodium valproate (SV) and lamotrigine (LTG) in treating refractory epilepsy (RE) in children and the predictive value of serum neuron-specific enolase (NSE) and central nervous system specific S100β protein (S100β) on efficacy assessment were explored. A total of 110 RE children admitted to Xuzhou Children's Hospital, Xuzhou Medical University were enrolled. Patients treated with SV alone served as the control group (n=51), and those treated with SV plus LTG as the study group (n=59). Serum NSE and S100β expression levels were measured by enzyme-linked immunosorbent assay (ELISA). The efficacy, seizure frequency, adverse reactions, concentration of serum brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF), and expression of serum NSE and S100β were observed and compared. The total effective rate in the study group was significantly higher than that in the control group, and the seizure frequency and incidence of adverse reactions were significantly lower than that in the control group. The study group showed remarkably higher BDNF and NGF than the control group after treatment. The expression of serum NSE and S100β in effectively treated children were significantly lower than that in ineffectively treated children. The area under the curve (AUC) of serum NSE and S100β were 0.828 and 0.814 respectively. SV combined with LTG is better and safer than SV alone in the treatment of RE in children. Serum NSE and S100β are of high value in predicting the efficacy.

we presented a case of drug-induced interstitial nephritis in a 43-year-old woman, having the history of renal calculi, as a result of sodium valproate and triamterene. Renal biopsy was used to confirm the diagnosis, however, due to poor prognosis along with discontinuation of drugs, she was treated with corticosteroids.

Background: Antiepileptic drug (AED) therapy has been claimed to deteriorate bone health. Majority of the research was inclined towards vitamin-D deficiency as the patho-mechanism. However, after the role of Wnt in bone metabolism was discovered, it has paved way for investigating the role of Wnt inhibitors in mediating effects on bone accrual. Recently, we have reported the modulation of two Wnt inhibitors, sclerostin and dickkopf-1 (DKK-1), following AED therapy in Indian women with epilepsy, however, the subgroup analysis for individual drug is elucidated in this report. Methods: Individual analysis for our earlier cross-sectional study on three AEDs, carbamazepine (CBZ), sodium valproate (SVP) and levetiracetam (LTM), on sclerostin and dickkopf-1, and their correlation with receptor activator of nuclear factor kappaB ligand (RANKL) and serum 25-hydroxy vitamin D (25OHD) was assessed in Indian women with epilepsy. Results: We observed enhanced sclerostin and 25OHD levels with all three AEDs while serum RANKL was higher with SVP and LTM only. Further, serum DKK-1 levels were lowered with CBZ and LTM. Sclerostin showed a positive correlation with RANKL in CBZ group, while DKK-1 presented no such relationship. Conclusion: As sclerostin is more specific than DKK-1, we may conclude that these drugs may compromise bone health through disturbance in Wnt signaling mechanisms.

Background & Objective: Although antiepileptic drugs have controlled the epilepsy attacks substantially, the side-effects are still considered as a problem to the patients. The aim of this study was to compare the effects of sodium valproate and carbamazepine on sexual function in men with epilepsy. Materials & Methods: In this cross-sectional study 35 male married epileptic patients with the history of taking carbamazepine for at least one year and 35 other male married patients using sodium valproate for at least one year have been participated. Both groups' sexual activity information has been evaluated by international index of erectile questionnaire. This fifteen question survey has investigated men's sexual activity in 5 fields such as erectile function, orgasmic function, sexual desire, intercourse satisfaction and overall satisfaction. Each question has 5 scores at most and the total score of the survey comes to 75.The results have been analyzed by Chi-Square and Mann-Whitney U tests using the statistical software SPSS (ver.16.0). Results: The average of total gained scores in sodium valproate takers was more than carbamazepine takers (51.68, 53.42) but there was no significant difference (p=0.582). Twenty-five sodium valproate takers (48.1%) and twenty-seven carbamazepine takers (51.9%) had erectile function disorder but there was no significant difference (p=0.584). The sodium valproate group average scores in all sexual activity fields except sexual desire was more than carbamazepine group but there was significant difference regarding only sexual desire. Conclusions: sexual activity disorders in men with epilepsy, especially erectile disorder were highly prevalent and also the result showed that patients who take sodium valproate had better status than carbamazepine takers regard to sexual activities except sexual desire.

Valproic acid, beside its anticonvulsant action, is widely used as a mood stabilizer in the therapy of bipolar disorder. The potential antidepressant action of valproic acid has not been sufficiently characterized so far. The aim of the present study was to evaluate the antidepressant effect of valproic acid in an aldosterone model of depression. Subchronic treatment with valproic acid resulted in a reduction of the time spent in immobility in the forced swim test. In conclusion, the present study provides evidence on antidepressant effects of valproic acid using a classical behavioral approach for testing the efficacy of antidepressant drug in animal models.

Objectives. To measure and compare free fraction of serum levels of VPA (valproic acid) between non-malnourished and malnourished epileptic children and to evaluate the adverse effects (myopathy, hepatotoxicity). Material and methods. It is a prospective comparative observational case control study in which forty epileptic children (malnourished: 18 male/8 female, age 8.3±2.5, non-malnourished: 8 male/6 female, age 8.1±2.1) who fulfilled the inclusion criteria were recruited as study group and twenty children as control group (12male/8 female, age 6.0±2.8). Outcome measures monitored are serum VPA levels (total and free fraction of serum VPA), serum CK (creatinine kinase), SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic-transaminase). Using screening tool for the assessment of malnutrition in pediatrics (STAMP©), subjects are categorized into mild, moderate, severe malnourished as -1SD, -2SD, -3SD respectively Outcomes. There is an elevation in mean free fraction of VPA is 17.3±6.4 μg/ml whereas in non-malnourished group it was found to be 8.7±4.2 μg/ml with P=

AIM To evaluate the utility of patch test and cross-sensitivity patterns in patients with adverse cutaneous drug reactions (ACDR) from common anticonvulsants. METHODS Twenty-four (M:F = 13:11) patients aged 18-75 years with ACDR from anticonvulsants were patch tested 3-27 mo after complete recovery using carbamazepine, phenytoin, phenobarbitone, lamotrigine, and sodium valproate in 10%, 20% and 30% conc. in pet. after informed consent. Positive reactions persisting on D3 and D4 were considered significant. RESULTS Clinical patterns were exanthematous drug rash with or without systemic involvement (DRESS) in 18 (75%), Stevens-Johnsons syndrome/toxic epidermal necrolysis (SJS/TEN) overlap and TEN in 2 (8.3%) patients each, SJS and lichenoid drug eruption in 1 (4.2%) patient each, respectively. The implicated drugs were phenytoin in 14 (58.3%), carbamazepine in 9 (37.5%), phenobarbitone in 2 (8.3%), and lamotrigine in 1 (4.7%) patients, respectively. Twelve (50%) patients elicited positive reactions to implicated drugs; carbamazepine in 6 (50%), phenytoin alone in 4 (33.3%), phenobarbitone alone in 1 (8.3%), and both phenytoin and phenobarbitone in 1 (8.33%) patients, respectively. Cross-reactions occurred in 11 (92%) patients. Six patients with carbamazepine positive patch test reaction showed cross sensitivity with phenobarbitone, sodium valproate and/or lamotrigine. Three (75%) patients among positive phenytoin patch test reactions had cross reactions with phenobarbitone, lamotrigine, and/or valproate. CONCLUSION Carbamazepine remains the commonest anticonvulsant causing ACDRs and cross-reactions with other anticonvulsants are possible. Drug patch testing appears useful in DRESS for drug imputability and cross-reactions established clinically.

Background Sodium valproate is a commonly used anticonvulsant. It is widely recognized that valproate can cause hyperammonemia, particularly in people with underlying liver disease. Patients with urea cycle disorders are genetically predisposed to this adverse event and can develop severe hyperammonemia if given valproate. This can occur even if liver functions tests and plasma concentration of valproate are normal, highlighting the importance of checking ammonia levels in any patient presenting with encephalopathy. Specific treatment for hyperammonemia must be implemented promptly. Case presentation A 22-year-old white British man with a history of epilepsy post head trauma presented with subacute encephalopathy 4 weeks after the introduction of sodium valproate. His ammonia levels were not checked until 48 hours into his presentation and were found to be elevated. He initially responded to treatment of his hyperammonemia and the raised levels were attributed to sodium valproate. However, as his ammonia levels continued to rise, further investigation led to a diagnosis of ornithine transcarbamylase deficiency. Conclusions Ornithine transcarbamylase deficiency is the most common of the urea cycle disorders. This case highlights both the importance of checking ammonia levels early and considering the diagnosis of this X-linked disorder in patients with raised ammonia, as these have implications both for the patient’s acute and further management, and for family screening.

Background Sodium valproate is one of the most widely used antiepileptics and mood stabilizers. However, this drug may induce acute pancreatitis. Few cases have been reported so far, mainly on the pediatric patients who underwent antiepileptic treatment. Hereby, we present a case of bipolar disorder with sodium valproate-induced acute pancreatitis. Case presentation The patient is a 54-year-old Chinese male. He was diagnosed with bipolar disorder for more than 39 years. Since the first onset of the disease, he had several relapses. The patient had had sodium valproate to stabilize mood swings for a year before the occurrence of acute pancreatitis. But he did vomit once during the inpatient care period. Then he was referred to another hospital following a notably high level of amylase. The results of computed tomography demonstrated an increased pancreatic volume and swollen peripancreatic fat tissue. As a result, the patient was diagnosed with acute pancreatitis. Unlike other cases reported in literatures, the high amylase level did not revert to normal after the withdrawal of medications. The patient was discharged from hospital with a high level of amylase, and was placed under follow-up observations. Conclusion Acute pancreatitis is considered as one of the idiosyncratic adverse reactions to antiepileptic drugs. Previous reports were mainly on the pediatric patients with increased propensity to idiosyncratic drug effects, or the adult chronic renal failure patients with sodium valproate-induced pancreatitis due to the retention of intermediate metabolites in their bodies. In this study, even though our patient exhibited no high risk of developing pancreatitis, he was treated for drug-induced acute pancreatitis in three hospitals. As rare as drug-induced acute pancreatitis can be, it should not be overlooked, Moreover, the mechanism of how sodium valproate induces acute pancreatitis remains unknown. Therefore, physicians need to consider the medical history of patients before prescribing this medication.

Background Radiculopathy due to lumbar or cervical disc disease is the most common chronic neuropathic pain in adults. The aim of present study was evaluation of low dose of sodium valproate on radicular pain and determining VPA pharmacokinetics. Materials and Methods In this double blind randomized placebo control clinical study, 80 patients with established lumbar or cervical radicular pain, have been randomly allocated into two study groups: 40 have received sodium valproate 200 mg/day and Celecoxib 100 mg/day and acetaminophen 500 mg PRN as rescue medication, and second group has received placebo, Celecoxib and acetaminophen. Quantitative assessment of pain was done by visual analogue scale (VAS) prior to perform the intervention and after ten days (treatment duration). Blood sample has been taken for determining mean through concentration after five half-lives. Evaluation of plasma concentration of VPA and that of efficacy on pain score relationship by comparing VAS before and after the therapy was done. Results Group A and B have demonstrated significant alleviation in mean VAS score; −21.97 ± 25.41, −14.39 ± 23.03 respectively (P < 0.001). The mean plasma concentration of VPA in group A was: 26.9 ±13.5 mg/L. Moreover, no significant correlation was seen between pain score with age, gender, and weight (p > 0.05). Conclusion Low dose of sodium valproate especially together with NSAIDs demonstrated good efficacy in lumbar and cervical radicular pain management.

Objective This study compared the efficacy and tolerability of sodium valproate and aripiprazole in the treatment of Tourette syndrome (TS). Method 24 children and adolescents with a diagnosis of TS from the Jiamusi Central Hospital between January 2014 and August 2017 were randomly divided into sodium valproate group and aripiprazole group according to the order of clinic visits and treated for 10 days. Tic severity was rated using the Yale Global Tic Severity Scale (YGTSS) and the Clinical Global Impressions Scale for tics (CGI-Tics) and the adverse reactions were valued using the Treatment Emergent Symptom Scale (TESS) at baseline and at each follow-up visit. Results The TTS score in the YGTSS scale decreased over time in both groups while the aripiprazole group was significantly higher on the 5th day (p p Conclusions The study indicates that the patients treated with sodium valproate injection have a faster onset time than the patients treated with oral aripiprazole in controlling tics.

International audience; PURPOSE: After a huge campaign of information on the teratogenic risk of sodium valproate (VPA) having taken place in France we aimed to evaluate the trend of its prescriptions in young epileptic girls.METHOD: Using the French National Health Insurance Database we searched for patients aged 0-14 years being supplied an antiepileptic drug (AED) between 2010 and 2016.RESULTS: 113,362 children received at least one AED, 61,259 boys and 52,103 girls. Compared to 2010-2014 years, VPA was less prescribed in 2016 as first AED (29% vs 37.3% respectively). The difference between the two periods was greater for girls (-41%) than for boys (-12%).CONCLUSION: The changing trend of VPA as first AED prescribed, particularly in girls, reflects published evidence in terms of safety.

Objective Epilepsy is a debilitating disease. Visual function changes have been reported and may be attributed to the epileptic changes or as a result of medication side effect. Sodium valproate and carbamazepine are both first line anti-epileptic medications used in Malaysian health care. Sodium valproate inhibits glutamate and γ-aminobutyric acid (GABA) transaminase while carbamazepine acts on the sodium channel - both are an important part of the retina. This study aimed to compare the visual functions of epilepsy patients on carbamazepine or sodium valproate monotherapy. Design A cross-sectional study was conducted at a tertiary hospital between June 2016 and November 2018. Methods Patients with idiopathic epilepsy that fulfill the inclusion and exclusion criteria were recruited from the neurology clinic. They were divided into two groups and underwent complete eye examinations. Visual functions such as color vision testing, contrast sensitivity, visual field and retinal nerve fiber layer measurement were subsequently performed. Statistical analysis was done using Statistical Package for the Social Science, version 24 (SPSS Inc, Chicago, IL, USA). Results A total of 100 patients (sodium valproate: 50 patients; carbamazepine: 50 patients) were recruited for the study. There were no statistically significant changes in anatomical or visual function between the sodium valproate and carbamazepine group. However, patients from both groups displayed color vision defect in the blue and green axes. Changes in color vision could indicate early retina toxicity secondary to the medication. Although there were no visual field changes, patients recorded a slight reduction of mean deviation. Changes of mean deviation could be attributed to the side effect of medication or the disease process. Conclusions Epileptic patients taking sodium valproate or carbamazepine did not demonstrate statistically significant change in visual function.

Background: An increased risk of impaired intelligence (IQ) has been documented in valproate-exposed children, but investigations have not previously focused on those with a clinical diagnosis of Fetal Valproate Syndrome (FVS). Methods: This cross sectional observational study recruited individuals with a diagnosis of FVS and completed standardized assessments of intellectual abilities making comparisons to a normative comparison group. Both mean difference (MD) and prevalence of scores below the lower average range were analyzed. Results: The mean full-scale IQ in 31 individuals with FVS (mean age 14.97; range 6–27 years) was 19 points lower (19.55, 95% CI −24.94 to 14.15), and IQ scores

WOS: 000504845000013 Sodium valproate is a well-known antiepileptic agent with multiple mechanisms of action such as sodium channel blockage and gamma-aminobutyric acid activity induction. Despite its well-described anxiolytic and mood stabilization effects, its mechanism of action in pathological gambling is not clear. However, it has been reported as an effective treatment option in pathological gambling for patients without Parkinson's disease (PD). We presented a male patient with a diagnosis of PD suffering from pathological gambling as an impulse control disorder due to antiparkinsonian drugs who did not respond to drug adjustments but showed complete improvement with sodium valproate, without any worsening in PD symptoms.

People with intellectual disability (ID) have a greater frequency of psychiatric illnesses, ranging from 10% to 80%, as compared to the general population. It has been proven that mood stabilizers are beneficial in the management of behavior issues in people with ID. Here, we report a series of five cases with mild and moderate ID with behavioral disturbances including mood and psychotic symptoms managed successfully with sodium valproate as the part of the treatment.

Introduction Chronic antiepileptic therapy has been associated with metabolic bone diseases including osteomalacia and osteoporosis. The aim of this study was to determine frequency of changes in biochemical and bone mineral density (BMD) in adults receiving valproaic acid (VPA) & carbamazepine (CBZ). Methods In a cross sectional study evaluating adults (age 20-50 y) epileptic patients receiving valproic acid or carbamazepine for at least 2 years. This study was conducted from May 2014 to May 2015 in Shahid Sadoughi Hospital of Yazd University of Medical Science, Yazd, Iran. Bone metabolism was evaluated by measurement of serum calcium (Ca), phosphorus (P), alkaline phosphatase (ALP) and parathormone hormone (PTH), BMD at lumbar and femoral measured by dual energy X ray absorptiometry (DXA). SPSS software (version 18) was used for data analysis. The t-test was used for quantitative data, and the chi-squared test was used for the qualitative variables. Results Eighty two epileptic patients (mean age: 31.67±10.69 year) treated with either carbamazepine (n=41) or valproate sodium (n=41) were studied. Normal serum Ca and P levels were observed in 98.8% and 97.6% of patients respectively. Serum ALP and PTH were normal in 97.6% and 97.6% of patients. Means of Ca and P in CBZ group were significantly lower than VPA group (Ca: 9.02 vs. 9.1, p-value: 0.03 and P: 3.54 vs. 3.76 p-value: 0.004). BMD values at lumbar spine were not significant in either group (T. score CBZ: -0.43± 0.744 vs. T. score VPA: -0.615± 0.904 and p-value: 0.333) and were significantly higher than Iranian normal population BMD value at femoral neck in CBZ group was lower than VPA group (T. score CBZ: -0.707± 0.896 vs. T. score VPA: - 0.297± 0.850 p-value: 0.04). Dosage of CBZ and VPA did not correlate with BMD and biochemical parameters. Duration of CBZ use had correlation with increased ALP and duration of VPA use had correlation with decreased BMD in adult patients. Conclusion long term anti-epileptic drug treatment either with CBZ and VPA which has unknown effects on skeletal mineralization and induces a state of decreased bone mineral density BMD values at femoral neck were significant in CBZ group Therefore regular screening for monitoring of biochemical markers of bone turnover and BMD with DXA during the treat period is recommended. In addition, Ca supplement could be considered for all patients with epilepsy upon initiation of CBZ and VPA therapy.

Tomoki Tada,1 Kensaku Aki,2 Wataru Oboshi,1,3 Kazuyoshi Kawazoe,4 Toshiyuki Yasui,5 Eiji Hosoi2 1Subdivision of Biomedical Laboratory Sciences, Graduate School of Health Sciences, Tokushima University, 2Department of Cells and Immunity Analytics, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 3Department of Medical Technology, Kagawa Prefectural University of Health Sciences, Kagawa, 4Department of Clinical Pharmacy Practice Pedagogy, Institute of Biomedical Sciences, 5Department of Reproductive and Menopausal Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan Background: The hyperfunction and activation of platelets have been strongly implicated in the development and recurrence of arterial occlusive disease, and various antiplatelet drugs are used to treat and prevent such diseases. New antiplatelet drugs and many other drugs have been developed, but some drugs may have adverse effects on platelet functions. Objective: The aim of this study was to establish an evaluation method for evaluating the effect and adverse effect of various drugs on platelet functions. Materials and methods: Human erythroid leukemia (HEL) cells were used after megakaryocytic differentiation with phorbol 12-myristate 13-acetate as an alternative to platelets. Drugs were evaluated by changes in intracellular Ca2+ concentration ([Ca2+]i) mobilization in Fura2-loaded phorbol 12-myristate 13-acetate-induced HEL cells. Aspirin and cilostazol were selected as antiplatelet drugs and ibuprofen and sodium valproate as other drugs. Results: There was a positive correlation between [Ca2+]i and platelet aggregation induced by thrombin. Aspirin (5.6–560µM) and cilostazol (5–10µM) significantly inhibited thrombin-induced increases in [Ca2+]i in a concentration-dependent manner. On the other hand, ibuprofen (8–200µM) and sodium valproate (50–1,000µg/mL) also significantly inhibited thrombin-induced increases in [Ca2+]i in a concentration-dependent manner. Furthermore, the interaction effects of the simultaneous combined use of aspirin and ibuprofen or sodium valproate were evaluated. When the inhibitory effect of aspirin was higher than that of ibuprofen, the effect of aspirin was reduced, whereas when the inhibitory effect of aspirin was lower than that of ibuprofen, the effect of ibuprofen was reduced. The combination of aspirin and sodium valproate synergistically inhibited thrombin-induced [Ca2+]i. Conclusion: It is possible to induce HEL cells to differentiate into megakaryocytes, which are a useful model for the study of platelet functions, and the quantification of the inhibition of thrombin-induced increases in [Ca2+]i is applicable to the evaluation of the effects of various drugs on platelets. Keywords: platelets, intracellular Ca2+ concentration ([Ca2+]i), aspirin, cilostazol, ibuprofen, sodium valproate

We describe a 29-year-old female who presented with rhabdomyolysis shortly after starting a course of sodium valproate. A thorough investigation revealed a likely mitochondrial origin inducing this susceptibility. An underlying mitochondrial disorder should be considered in all patients who present with undifferentiated disease whilst taking sodium valproate.

Aims and Objectives: To test anticonvulsant properties of three medicinal plants with pentylenetetrazole induced seizure test in Swiss albino mice. Materials and Methods : Herbs selected for the work (leaves of Aegle marmelos , seed of Nigella sativa , and fruit of Benincasa hispida) were collected locally from Mangalore, India and were authenticated by a Taxonomist. Aqueous extract of Aegle marmelos leaves (AmAE) and Ethanolic extract of Nigella sativa seeds (NsEE) were prepared by Soxhlet extraction and separated from solvent using a water bath. Benincasa hispida fruit juice (BhE) was filtered and dried on a water bath. Qualitative phytochemical analysis of the test extracts were done with Preliminary chemical reaction tests, and Liquid chromatography–mass spectrometry (LC/MS). Male Swiss albino mice, 3-4 months of age, weighing 25-30g were used in the study. Extracts and vehicle were administered orally 1 hour prior to inducing convulsions. Test employed for screening anticonvulsant properties was Pentylenetetrazole (PTZ) induced seizure test [60mg/kg/i.p]. Animals were treated with extracts at a dose of 900mg/kg orally. The results were compared with control group and test for analysis of variance and significance were done (ANOVA, Dunnett’s test). Results: Aqueousextract of Aeglemarmelos leaves and Ethanolic extract of Nigella sativa seeds possess anticonvulsant property in Pentylenetetrazole (PTZ) induced seizure model, Crude extract of Benincasahispida fruits did not show statistically signifi cant anticonvulsant property. Conclusions: Aeglemarmelos leaf and Nigella sativa seed possess anticonvulsant properties in pentylenetetrazole induced seizures, this is in accordance with many other published reports on the same herbs with different animal models and indicates effectiveness in human absence seizure patients. Asian Journal of Medical Sciences Vol. 7(3) 2016 97-102

The present study aimed to compare the clinical efficacy of donepezil combined with quetiapine and with sodium valproate on behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer's disease (AD), and to explore the changes and clinical value of vascular endothelial growth factor (VEGF). For this purpose, a total of 131 patients with AD admitted to the Infirmary of Shandong Agricultural University from January, 2017 to January, 2019 were included, of which 60 treated with donepezil combined with quetiapine were designated as group A, whereas 71 treated with donepezil combined with sodium valproate were designated as group B. The behavioral pathology in the AD rating scale (BEHAVE-AD) was used for the evaluation of the clinical efficacy, the brief psychiatric rating scale (BPRS) for the mental state assessment, and the mini-mental state examination (MMSE) for the assessment of cognitive performance. Any adverse reactions were recorded, and the treatment costs of the drugs were compared. According to the treatment efficacy, the patients were divided into the excellent efficacy group and the poor efficacy group. No significant differences were observed in clinical efficacy, or in the single and total adverse reactions between the 2 groups (P>0.05). The drug treatment costs in group A were significantly higher than those in group B (P

Background:Sodium valproate (VPA) is considered as the drug of choice for the treatment of generalized epilepsy in children. Sodium Valproate may be hepatotoxic.Aim:To assess the level of derangement of liver enzymes in children with epilepsy on treatment with sodium valproate.Methods:A cohort study. One hundred fifty-three children, comprising 51 with epilepsy on treatment with VPA (group I), 51 with epilepsy on treatment with other antiepileptic drugs (AEDs) but not VPA (group II), and 51 with nonconvulsive disorders (group III) had liver function tests performed for them. Data were analyzed by SPSS version 23.0.Results:There were 85 males and 68 females, aged 6 months to 14 years (median = 7.0 years). There was no significant difference in the mean plasma levels of alanine transaminase (ALT), alkaline phosphatase, and gamma glutamyl transferase across the three groups of children. The mean aspartate transaminase level was significantly higher in children in group III. There was a statistically significant negative correlation between the duration of AED therapy and the mean serum level of AST ( r = −0.266, P = 0.016). The serum ALT level showed a statistically significant positive correlation with the duration of AED therapy ( r = 0.268, P = 0.015).Conclusion:Sodium valproate monotherapy does not appear to be associated with significant hepatotoxicity in children in our cohort.

Carbamazepine and sodium valproate are one of the most common antiepileptic medications used in clinical practice. The period of treatment is commonly associated with benign alternation of the liver enzymes due to drug metabolism. Evaluation of asymptomatic enzymatic changes could be challenging to the expert clinician and may expose patients to unnecessary procedures or expenses. Thus, this article aims to focus on the frequency of liver enzyme abnormalities among epileptic children. For this, an analytic cross-sectional study was conducted in 100 epileptic patients who received carbamazepine or sodium valproate for 1 year. Those with healthy pretreatment liver enzymes were recruited for the study. The results showed an elevation of Aspartate Aminotransferase (AST) in 24% of the patients treated with sodium valproate (p = 0.01) and 20% of the patients treated with carbamazepine. Alanine Aminotransferase (ALT) was elevated in both groups to a similar extent, 6% (p = 0.01). In conclusion, the study showed a lower proportion of liver enzyme abnormalities, since AST is a less sensitive biomarker when compared to ALT. No measurement exceeds twice the average value, nor are there any clinical abnormalities. There is no proven value of routine liver enzyme measurement in asymptomatic patients in our study. However, baseline enzyme tests are recommended. Further controlled studies on a larger sample size are required.

ObjectivesIn November 2014, the CMDh (a regulatory body representing EU Member States) advised doctors not to prescribe sodium valproate for epilepsy or bipolar disorder in preg nant women, in women who can become pregnant, or in girls unless other treatments are ineffective or not tolerated. This study aimed to determine if this warning led to changes in prescription patterns.Design and settingCohort of 5.4 million women aged between 10 and 50 years identified in electronic health care data from United Kingdom, France, and Italy (2007–2016).Main outcome measuresAnti‐epileptic drug (AED) prescriptions.ResultsThe prevalence of women receiving AED prescriptions in 2016 varied from 12.2 per 1000 to 29 per 1000 in the four regions. The incidence of prescribing any AED (excluding clonazepam, gabapentin, and pregabalin) fell each year on average by 7.5% (95% CI, 7.0%‐8.0%; Emilia Romagna), 9.6% (8.3%‐11.0%; France), 7.1% (6.7%‐7.6%; Tuscany), and 0.4% (0.2%‐1.0%; United Kingdom). The relative odds of prescribing sodium valproate rather than any other AED decreased more after 2014 compared with before the end of 2014 in France (OR = 0.77; 95% CI, 0.60‐0.98), Tuscany (0.81; 0.76‐0.86), Emilia Romagna (0.83; 0.76‐0.90), and the United Kingdom (0.92; 0.80‐1.06; not statistically significant).ConclusionsThere is evidence that the CMDh warning did lead to changes in prescription patterns of sodium valproate in women of childbearing age. There were considerable differences in prescribing practice amongst regions of Europe.

Ранее было установлено, что в ответ на резкое снижение атмосферного давления у крыс линии КрушинскогоМолодкиной (КМ) возникает двигательное возбуждение, переходящее в клоникотонический судорожный припадок гипобарическая эпилептиформная реакция (ГЭР). Цель исследования. Подтвердить пригодность ГЭР у крыс линии КМ для тестирования антиконвульсантов. Методика. Для моделирования ГЭР крыс помещали в индивидуальную проточную барокамеру, снабженную высотомером, и поднимали с помощью вакуумнасоса до высоты 5000 метров со скоростью 50 м/с (декомпрессия). В процессе подъема у крыс возникала ГЭР. Антиконвульсанты карбамазепин и вальпроат натрия вводили крысам внутрибрюшинно в дозе 30 мг/кг и 200 мг/кг соответственно. Параметры ГЭР оценивали до и после введения антиконвульсантов. Результаты. Показано, что через 11,5 часа после введения антиконвульсантов ГЭР наблюдалась лишь у 30 и 40 крыс, при этом высота (в метрах) начала двигательного возбуждения увеличивалась и снижалась тяжесть припадка в баллах. У остальных крыс наблюдалось полное отсутствие ГЭР. Протекторный эффект карбамазепина исчезал через 24 часа после его инъекции, тогда как протекторный эффект вальпроата натрия через 24 часа сохранялся у 50 крыс. Заключение. На модели рефлекторной эпилепсии, вызываемой вакуум декомпрессией, установлено, что карбамазепин и вальпроат натрия одинаково эффективны через 11,5 часа после их введения, однако вальпроат натрия оказывал более пролонгированный протекторный эффект по сравнению с карбамазепином. ГЭР у крыс КМ может быть использована в качестве экспериментальной модели для тестирования антиконвульсантов., Previously it was found that KrushinskyMolodkina (KM) rats responded to a sharp decline in atmospheric pressure with a hypobaric epileptiform reaction (HER), motor excitation resulting in tonicclonic seizure. The aim of the study was to confirm that HER was suitable for testing anticonvulsants in KM rats. Methods. Carbamazepine and sodium valproate were administered to rats intraperitoneally at doses of 30 mg/kg and 200 mg/kg, respectively. For modeling HER, rats were placed in an individual chamber equipped with an altimeter and elevated to a simulated altitude of 5,000 m at a speed of 50 m/sec using a vacuum pump. In the process of elevation, rats developed HER. The HER parameters were evaluated before and after the anticonvulsant administration. Results. In 11.5 hours after administration of the anticonvulsants, carbamazepine and sodium valproate, HER was observed only in 30 and 40 of rats. Furthermore, the altitude in meters of the motor excitation onset was increased whereas the seizure severity in scores was decreased. The rest of the rats had no signs of HER. The protective effect of carbamazepine disappeared at 24 hours after the injection while the protective effect of sodium valproate remained in 50 of rats. Conclusion. Using a model of reflex epilepsy induced by vacuum decompression, carbamazepine and sodium valproate were shown to be equally effective in 11.5 hours after their administration however, the protective effect of sodium valproate stayed longer than that of carbamazepine. HER in KM rats can be used as an experimental model for testing anticonvulsants., №3 (2019)

Background Despite significant teratogenic risks, sodium valproate is still widely prescribed in many countries to women of childbearing age, as a mood stabiliser in bipolar disorder and also in epilepsy. The UK has recently banned valproate use in women who are not in a pregnancy prevention programme. Whilst this ruling reflects prevailing clinical practice, it also highlights an ongoing debate about when (if ever) a woman who is or could become pregnant should be allowed to choose to take valproate. Main body We review the benefits and harms of drugs available for bipolar disorder and epilepsy in women of childbearing age, with a particular focus on teratogenic risk. We speculate on hypothetical rare situations in which potential benefits of valproate may outweigh potential harms in such women. We also review the literature on shared decision-making – on which there is now a NICE guideline and numerous evidence-based decision tools. Drawing on previous work by experts in shared decision-making, we offer a list of ‘frequently asked questions’ and a matrix of options to support conversations with women about continuing or discontinuing the drug in (or in anticipation of) pregnancy. We also consider whether shared decision-making is an appropriate paradigm when considering whether to continue a teratogenic drug. Conclusion We conclude that because valproate in pregnancy remains the subject of such debate, there is scope for further research – not only into the relative efficacy and safety of alternatives to it – but also into the dynamics of communication and shared decision-making in this situation.

Women with epilepsy need to continue to take anticonvulsants during their pregnancies to prevent seizures from occurring. Since the 1980's, it has been known that the use of valproate (an anticonvulsant) in the first trimester of pregnancy is associated with an increased risk of spina bifida. Recent studies have also demonstrated increased risks of other congenital anomalies as well as a risk of cognitive impairment. Doctors in the EU are now advised not to prescribe valproate in pregnant women, in women who can become pregnant or in girls unless other treatments are ineffective or not tolerated. This study aimed to determine if there has been a reduction in the numbers of babies born with valproate syndrome in Europe from 2005 to 2014. Data from 15 European congenital anomaly registries, who are members of EUROCAT (A European network of population-based registries for the epidemiologic surveillance of congenital anomalies), identified 28 cases of valproate syndrome in 2.74 million births from 2005 to 2014. The prevalence of valproate syndrome in Europe significantly decreased from 0.22 per 10,000 births in 2005/6 to 0.03 per 10,000 births in 2013/14. One registry, Ile de la Reunion, had the majority of cases (17). After excluding these cases there still remained a decreasing trend even though it no longer reached statistical significance due to the small number of cases. This study emphasises the continued need for European collaboration in analysing rare exposures and rare anomalies.

Background Status epilepticus (SE) is a neurological emergency which can be life‐threatening. Several medical regimens are used in order to control it. In this study, we intended to evaluate the clinical efficacy and tolerability of sodium valproate and intravenous phenytoin (IV PHT) in the control of SE. Methods One hundred and ten consecutive patients suffering from benzodiazepine refractory SE who were referred to the emergency ward from March 2014 to March 2015 were randomly divided into two groups. The first group received intravenous sodium valproate, 30 mg/kg as loading dose and then 4–8 mg/kg every 8 hr as maintenance regimen. The second group received IV PHT 20 mg/kg as loading dose and then 1.5 mg/kg for 8 hr as maintenance therapy. All patients were monitored for vital signs every 2 hr up to 12 hr. The patients were also followed up for 7 days regarding drug response and adverse effects. Results The administration of sodium valproate and phenytoin respectively resulted in seizure control in 43 (78.18%) and 39 (70.90%) of the patients within 7 days of drug administration (p = .428). Seven‐day mortality rate was similar in both groups (12.73% vs. 12.73%; p = .612). There was no significant difference in adverse effects between two groups. Conclusion Sodium valproate is preferred to IV PHT for treatment and control of SE due to its higher tolerability and lower hemodynamic instability.

PubMed ID: 29315457 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 .05). BAT/BAE ratios were low both in VPA and CBZ groups (P

Objective : Convulsive status epilepticus (CSE) is very rarely observed after ischaemic stroke. Sodium valproate (SV) is one of the agents used in the treatment of CSE, but its role still controversial, and its degree of efficacy in treating CSE that develops following stroke is unclear. Method : We evaluated 19 patients who were treated with intravenous (IV) SV (20 mg/kg, 2 mg/kg/h-12h) after diazepam. Patients’ modified Rankin scores (mRS), SE types, and changes in biochemical parameters after treatment were assessed. Results : CSE was successfully treated in 12 (63.15%) patients. Side effects such as hypotension and allergic reactions were observed in two patients. Refractory SE development was observed in 5 (29.4%) patients with high mRS (˃ 3). No significant deterioration in patients’ laboratory evaluations, conducted before and after status, was observed. Conclusion : SV may be safe and effective in the treatment of CSE observed after ischaemic stroke, especially in patients with low mRS.

Background: The primary objective of the present study was to evaluate the efficacy and safety of using acupressure as an adjunctive therapy to sodium valproate (SV) combined with acupressure (ASV) on the prevention of chronic migraine with aura (CMA). Methods: A total of 98 patients with CMA were randomly divided into an intervention group and a control group, with 49 patients in each group. The patients in the intervention group received ASV, while the participants in the control group received SV alone. The primary outcome was measured by the numeric rating scale (NRS). The secondary outcomes including frequency of migraine attacks, the times of using analgesics, and quality of life, measured by the short-form 36 Health Survey Scale (SF-36) score. In addition, adverse events (AEs) were also recorded throughout the trial. The outcomes were measured at the end of the 8-week treatment, and 4-week follow-up. Results: After the 8-week treatment and 4-week follow-up, ASV efficacy was not greater than that of SV alone regarding pain relief, as measured using the NRS, and frequency of migraine attacks, consumption of analgesics, and quality of life, as measured using the SF-36. However, ASV can significantly reduce the nausea when compared with SV (P = .04). Conclusion: The present results indicate that ASV can decrease migraine-related nausea during treatment, but cannot relieve pain or enhance quality of life in patients with CMA.