Dose Of Sodium Valproate Research Articles

An observational case-control study comparing the recovery profile in patients receiving additional dose of anticonvulsant vs. regular dose during supratentorial craniotomy.

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.

Evaluation of Dose Related Structural Changes in Sodium-Valproate-Induced Hepatotoxicity and a Possible Protective Role of Vitamin E in Adult Albino Rats

Background: Sodium valproate (SV) is a widely administered antiepileptic drug, although hepatotoxicity is a side effect. Vitamin E (vit. E) being a potent antioxidant agent and essential fat-soluble nutrient that can dramatically decreased this hepatotoxic effect.Aim of the Work: To investigate the histopathological and ultrastructural changes caused by different doses of SV, observe their correlations with liver biomarker levels and assess the defensive role of vit. E against SV-hepatotoxicity.Methods: Sixty male adult albino rats were randomly divided into six groups. Group 1 was treated with normal saline. Group 2 was treated orally with vit. E (100 mg/kg/day). Groups 3, 4 and 5 were treated intraperitoneally with SV at doses of 100, 300 and 500 mg/kg/day, respectively, for 8 consecutive days. Group 6 was treated intraperitoneally with SV (500 mg/kg/day) and orally with vit. E (100 mg/kg/day) for 8 consecutive days. On the ninth day, blood samples were collected to assess the biochemical markers of the liver, and the results were statistically analysed. The rats were deeply anaesthetized and sacrificed. Liver specimens were carefully dissected, and portions were fixed in 10% formalin solution for histopathological examination; others were fixed in 2.5% glutaraldehyde for ultrastructural study.Results: The liver function among the different groups was found to be significantly changed in dose dependent manner. Histopathological examination showed gradual distortion of hepatic lobular architecture and infiltration of lymphocytic cells. Concerning hepatocyte ultrastructure, SV was a destructive compound for most intracellular organelles. This toxicity was most obvious in the groups treated with higher doses; however, concurrent administration of vit. E with SV provided some hepatoprotection.Conclusion: SV is a destructive compound to the liver architecture, especially in high doses. However, SV damage can be attenuated by concurrent administration of vit. E, which considerably decreases most SV-induced hepatotoxicity.

Sodium Valproate Improves Skin Flap Survival via Gamma-Aminobutyric Acid and Histone Deacetylase Inhibitory System

Sodium valproate interacts with biological systems through different mechanisms such as activation of gamma-aminobutyric acid (GABA)-sensitive chloride channels and inhibition of histone deacetylase. In this study, we examined the effect of sodium valproate in random-pattern skin flap of rats and investigated its mechanisms of action. Different types of experiments were carried out. In acute treatment, different doses of sodium valproate (50, 100, 150, 300 mg/kg) were injected intraperitoneally 1 h before surgery. In chronic treatment, the substance was injected each day for 2 wk. The size of skin necrosis was measured 1 wk after the surgery. The rate of secondary healing, amount of weight gain, hair growth, and wound regeneration were measured 2 wk after operation. In acute treatment, sodium valproate (100 mg/kg) reduced significantly the length of skin necrosis (P < 0.05). Administration of bicuculline (competitive antagonist of GABAA, 20 mg/kg) increased the length of skin necrosis (P < 0.05). In addition, administration of 100 mg/kg of sodium valproate and subeffective dose of bicuculline (10 mg/kg) prevented the protective effect of sodium valproate on skin flap necrosis (P < 0.05). In the chronically treated skin flap group, 100 mg/kg of sodium valproate reduced the length of necrosis (P < 0.01). Weight gain in the valproate group was more than that in the control group (P < 0.05). Skin also healed faster in the sodium valproate group than in the control group (P < 0.001). Combination therapy of sodium valproate and trichostatin A (330 nmol/kg) reversed the effect of valproate (P < 0.05). This study demonstrate that sodium valproate accelerates skin secondary healing in a rat model of skin flap probably through a GABA and histone deacetylase–dependent mechanism.

Anticonvulsant activity of Adhatoda vasica leaves by pentylenetetrazol model: preliminary evaluation in rats

Background: Epilepsy is a disorder characterised by recurrent seizures of cerebral origin with episodes of sensory, motor phenomenon with or without loss of consciousness. The present study was taken up to evaluate the anticonvulsant effect of aqueous extract of leaves of Adhatoda vasica in rats. Objectives of this study is to evaluate the effect of aqueous extract of Adhatoda vasica leaves on Pentylenetetrazol induced seizures in albino rats and to compare the effect of aqueous extract of Adhatoda vasica leaves with standard dose of sodium valproate on Pentylenetetrazol induced seizures in albino rats.Methods: Anticonvulsant activity of aqueous extract of Adhatoda vasica was analysed using PTZ (Pentylenetetrazol) model. Groups used were distilled water as control group, Sodium valproate as standard for Pentylenetetrazol and two doses of aqueous extract of Adhatoda vasica (100mg/kg and 200 mg/kg) for this screening model. Parameters observed for PTZ models were abolition of clonic seizures and time duration between injection of PTZ and onset of seizures.Results: In PTZ model, test group at 200 mg/kg showed 33.33% protection for abolition of clonic seizures, though not comparable to standard group. There was significant increase in the duration of onset of clonic seizures after PTZ injection in both test groups (at 100 mg/kg and 200 mg/kg) when compared to control group.Conclusions: Aqueous extract of leaves of Adhatoda vasica has shown significant anticonvulsant action in PTZ model.

Effect of calcium channel blocker as anticonvulsant and its potentiating effect when used along with sodium valproate in pentylenetetrazole induced seizures in Albino rats

Background: Many antiepileptic drugs were introduced for the treatment of epilepsy. Ideal antiepileptic drug should not only prevent but also correct the underlying pathophysiology without altering the normal neurotransmission. Calcium channel blockers may form such group because initiation of seizure is associated intrinsic burst firing which is triggered by large inward calcium current, so this study was done to evaluate the anticonvulsant effect of amlodipine in albino rats.Methods: A total of 42 adult albino rats were included in the study and divided into 7 groups, each containing 6 rats. Group 1 received distilled water, group 2,3 received sodium valproate 50mg/kg and 100mg/kg, group 4-6 received amlodipine 1, 2, 4mg/kg and group 7 received combination of Amlodipine 1 mg/kg and sodium valproate 50mg/kg. Pentylenetetrazole induced seizures model was done and onset of myoclonic jerks, onset of clonic convulsions and duration of clonic convulsions was studied.Results: There was a significant anticonvulsant effect in Amlodipine doses 2, 4mg/kg (p &lt;0.001). The combination of Amlodipine (1mg/kg) and Sodium valproate (50mg/kg) also had significant anticonvulsant effect.Conclusions: Amlodipine, a calcium channel blocker has anticonvulsant effect and also potentiated the anticonvulsant effect of low dose sodium valproate.

Sodium valproate enhances doxorubicin-induced cognitive dysfunction in Wistar rats

BackgroundIncreasing number of scientific reports have highlighted the role of histone acetylation/deacetylation in neurodegenerative conditions, including chemotherapy-induced cognitive dysfunction (also known as chemobrain). Multiple sources state that increased activity of histone deacetylases (HDACs) play a detrimental role in chemobrain. In the present study, sodium valproate, a well-known HDAC inhibitor, was explored for its neuroprotective potential against chemobrain development. MethodsDoxorubicin (DOX), a chemotherapeutic agent, was used to induce chemobrain in experimental animals while treating with sodium valproate simultaneously. The animals were subjected to novel object recognition test (NORT) in order to assess their cognitive status and further, brain antioxidant levels were estimated. The animal body weights and survival were noted throughout the period of the study. Blood parameters such as red blood cell count, white blood cell count and haemoglobin levels were also measured. ResultsOur findings are in contradiction to the known neuroprotective properties of valproic acid. We observed that sodium valproate failed to prevent chemobrain development in DOX treated animals. In fact, treatment with sodium valproate dose dependently worsened cognitive status in DOX treated animals including their brain antioxidant status, possibly leading to neuronal damage through free radical induced toxicity. ConclusionThe present study highlights the caution that needs to be exercised in projecting HDAC inhibitors as in vivo neuroprotective agents, due to the complexity of existing neurological pathways and the diverse roles of histone deacetylases.

Association of Insulin Resistance with Sodium Valproate Therapy among Epileptic Patient

Background: Epilepsy is a common neurological disorder. Sodium valproate is one of the commonest broad spectrum antiepileptic drugs and it is used worldwide. Weight gain is the common side effect which is known to be associated with insulin resistance. The aim of this study was to see the association of sodium valproate therapy with insulin resistance among epileptic patients.&#x0D; Methods: It was a cross-sectional analytical study. Total 102 patients (51 epileptic patients with valproate monotherapy for at least one year and another 51 age and sex matched newly diagnosed epileptic patients without any anti-epileptic drugs) were selected in this study. The study was carried out from March 2016 to April 2017 for one year in the epilepsy clinic and outpatient Department of Neurology at Bangabandhu Sheikh Mujib Medical University, Dhaka. Participants underwent anthropometric evaluations and biochemical tests including fasting blood sugar and fasting insulin level. Insulin resistance (IR) index was calculated.&#x0D; Result: In this study mean duration of valproate treatment was 3.12±1.26 years and mean sodium valproate dose was 1133±440.5 mg/day (17.7±6.65 mg/kg/day). This study revealed serum fasting insulin level in valproate group and non-valproate group was 11.05±4.86 (ìU/ml) and 7.39±2.01 (ìU/ml) respectively. Fasting blood glucose was 4.71±0.79 (mmol/L) in valproate group and 4.41±0.62 (mmol/L) in non- valproate group. Calculated IR index in valproate group and non-valproate group was 2.17±0.55 and 1.46±0.39 respectively. IR index, fasting insulin and blood glucose all were significantly higher in valproate group than non- valproate group. This study also revealed mild positive correlation of IR index with dose and duration of valproate treatment.&#x0D; Conclusion: Sodium valproate treated patient had significantly higher IR index than control group.&#x0D; Bangladesh Journal of Neuroscience 2017; Vol. 33 (2): 63-69

Evaluation of a human neural stem cell culture method for prediction of the neurotoxicity of anti-epileptics.

Human neural stem cells have been proposed as an in vitro model to predict neurotoxicity. In this study, the potential of in vitro cultures of human-derived neurospheres to predict the effects of various anti-epileptic drugs (sodium valproate, phenytoin, carbamazepine and phenobarbitone) was evaluated. In general, these drugs had no significant effects on cell viability, total cellular protein, and neuronal process length at low doses, but at high doses these parameters were reduced significantly. Therapeutic doses of sodium valproate and phenytoin had a clear effect on neurosphere size and cell migration, with a significant reduction in both parameters when compared with the control group. The other drugs (carbamazepine and phenobarbitone) reduced neurosphere size and cell migration only at higher doses. The expression levels of glial fibrillary protein and tubulin III, which were used to identify astrocytes and neuronal cells, respectively, were reduced in a dose-dependent manner that became significant at high doses. The levels of glial fibrillary protein did not indicate any occurrence of reactive astrocytosis.

Valproate used during pregnancy: What should be done?

BackgroundSodium valproate can cause serious developmental disorders in unborn babies if taken while pregnant, especially in the first trimester.AimTo review recent literature and advice or treatment for women who have or are using valproate whilst pregnant.DesignLiterature review.MethodsLiterature review using Pubmed with search terms: ‘bipolar’; ‘pregnant’; ‘valproate’ and following up references.ResultsThere are several small methodologically flawed studies that attempt to address this question and will be reprised. Three key population register studies found high rates of malformations. A retrospective study of longer-term outcomes found high rates of developmental issues. There are several relevant treatment guidelines, including from the National Institute for Health and Clinical Excellence (NICE). There is a 40% risk of developmental disorder, a 10% risk of congenital malformations and a 3% risk of IQ deterioration.ConclusionsAvoid valproate in women of childbearing age if at all possible, and consider effective contraception if used. If already pregnant then consider, with involvement from the patient, stopping or minimizing the dose of sodium valproate. Assess the risks and benefits of using sodium valproate during pregnancy versus stopping the treatment for the first trimester as symptoms of the disorder may return. Seek advice from a perinatal psychiatrist. Add 5 mg of folic acid daily for the remainder of the pregnancy.Disclosure of interestThe authors have not supplied their declaration of competing interest.

The beneficial effects of l-cysteine on brain antioxidants of rats affected by sodium valproate.

Oxidative stress caused by sodium valproate (SV) is known to play a key role in the pathogenesis of brain tissue. The present study was designed to evaluate the protective effect of l-cysteine (LC) on the antioxidants of brain tissue of rats. The animals were divided into six groups: control group 1 was treated with saline as vehicle, groups 2 and 3 were treated with low and high doses of SV (100 and 500 mg/kg, respectively), group 4 was treated with LC (100 mg/kg), and groups 5 and 6 were treated with low-dose SV + LC and high-dose SV + LC, respectively. All the groups were treated orally by gastric tube for 30 successive days. Some antioxidant parameters were determined. Brain tissue (cerebral cortex) of SV-treated animals showed an increase in lipid peroxidation (LPO) and reduction in activity of enzymatic antioxidant and total antioxidant levels. Histopathological examination of cerebral cortex of SV rats showed astrocytic swelling, inflammation, and necrosis. After 4 weeks of the combination treatment of SV and LC daily, results showed significant improvement in the activity of cathepsin marker enzymes and restored the structure of the brain. LC was able to ameliorate oxidative stress deficits observed in SV rats. LC decreased LPO level and was also able to restore the activity of antioxidant enzymes as well as structural deficits observed in the brain of SV animals. The protective effect of LC in SV-treated rats is mediated through attenuation of oxidative stress, suggesting a therapeutic role for LC in individuals treated with SV.

To evaluate the anti-kindling effect of allopregnanolone alone and its interaction with sodium valporate in pentylenetetrazole induced kindling model

Background and purposeStudies in the animal models of epilepsy have suggested the anti-seizure effects of neuroactive steroids and its derivatives in kainic acid and pilocarpine induced limbic seizures and status epilepticus in mice, but no such studies have been reported in the published literature on the role of allopregnanolone in chemical kindling model and its interaction with sodium valproate. The purpose of this study was to evaluate the interaction between sodium valproate and allopregnanolone in pentylenetetrazole induced kindling model in rats. MethodsIn a PTZ kindled Wistar rat model, sodium valproate and allopregnanolone were administered 30min before the PTZ injection. The PTZ injection was given on alternate day till the animal became fully kindled or till 10 weeks. The parameters measured were latency to develop kindling and incidence of kindling, histopathological study of hippocampus, hippocampal anti-oxidant parameters and hippocampal DNA fragmentation studies. ResultsIn this study, the combination of low dose of allopregnanolone with low dose of sodium valproate showed a similar beneficial effect to that of a higher dose of sodium valproate in significantly reducing the number of kindled animals (0/8) as compare to PTZ control group (5/8) as well as the seizure scores and the histopathological scores. The combination significantly reduces oxidative stress by significantly decreasing the MDA levels, and increasing the SOD levels and GSH levels in the hippocampus of rats as compared to PTZ control group. So all these data suggest the antiepileptic effect of the combination and confers the synergistic interaction between the allopregnanolone and sodium valproate. ConclusionsIt can be concluded that by choosing this combination the dose of sodium valproate can be reduced and thereby reduces the incidence of adverse effects caused by sodium valproate and hence proves to be a useful combination clinically. This study has lead the basis to further investigate the various combinations of neurosteroids and valproate in the process of epileptogenesis with better side effect profile.

Nephrotoxicity of sodium valproate and protective role of L-cysteine in rats at biochemical and histological levels.

This study investigated whether the combination of sodium valproate (SV) with L-cysteine (LC) can decrease the SV toxicity of kidneys. SV caused alternation in oxidative/antioxidant balance. Biochemical estimations included the determination of oxidative stress markers like thiobarbituric acid-reactive substances in kidney tissue, and enzymatic antioxidant activities such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase as well as total antioxidant capacity were evaluated in renal tissues. Creatinine and uric acid levels in the serum were also determined to assess kidney function. Pathological examination of the kidney was also performed. Increasing the levels of lipid peroxidation and decreasing the enzymatic activity (SOD, CAT, and GPx) as well as total antioxidant capacity of rats was shown with different doses of SV. Impairment in renal function tests suggests a decreased glomerular filtration rate, as serum creatinine was elevated. Histopathological changes of kidney tissue treated with SV reveal the proximal and the distal convoluted tubules that show hydropic changes (small white vacuoles within the cytoplasm and the glomeruli show hypercellularity). The concurrent administration of LC with SV significantly had beneficial effects on the kidney and all the above parameters have been improved.

Valproate-induced hyperammonemic encephalopathy in an elderly patient with bipolar disorder

Hyperammonemia is a rare side effect of valproate, diagnosis of which requires a high level of clinical suspicion. We describe a case of 57-year-old man, suffering from bipolar affective disorder, who had multiple physical comorbidities (diabetes mellitus, benign prostatic hyperplasia, hydroureteronephrosis, and chronic kidney disease) and was on sodium valproate 1500 mg/day along with risperidone 6 mg/day, who developed delirium when the dose of sodium valproate was increased from 1500 mg/day to 2000 mg/day. In view of use of high doses of valproate, hyperammonemia was suspected, and on investigations, patient was found to have high ammonia levels (159 μmol/l). He was managed conservatively with stoppage of valproate and syrup lactulose. To conclude this case depicts that use of high doses of valproate can lead to hyperammonemia, especially among those with chronic medical illnesses.

EFFECT OF SODIUM VALPROATE AND DOCOSAHEXAENOIC ACID ON INFLAMMATION IN RATS

ABSTRACTObjective: To evaluate the anti-inflammatory activity of sodium valproate and docosahexaenoic acid (DHA) supplementation using variousexperimental models in albino Wistar rats.Method: A total of 48 adult Wistar albino male rats were divided into 8 groups of 6 rats each. Group I was control (distilled water 1 ml/kg), Group IIreceived intraperitoneal (i.p.) injection of indomethacin (10 mg/kg), Groups III-V were injected (i.p.) with sodium valproate 100, 200, and 400 mg/kgwater, and Groups VI-VIII were given sodium valproate 100, 200, and 400 mg/kg plus DHA 300 mg/kg (i.p.), respectively. Anti-inflammatory activitywas assessed using carrageenan induced paw edema and the cotton pellet granuloma models.Results: We found that higher doses of sodium valproate (400 mg/kg) used either alone or with a combination of DHA (300 mg/kg) showed asignificant anti-inflammatory activity when compared to control in both the models of inflammation.Conclusion: Combination of sodium valproate along DHA has shown promising anti-inflammatory activity.Keywords: Anti-inflammatory drugs, Sodium valproate, Rat model.

Combined Blockade of AMPA and NMDA Receptors Produces Maximal Suppression of the Development of Corasol Kindling in Rats

Chronic enteral administration of the standard antiepileptic drug sodium valproate at a dose of 200 mg/kg suppressed the development of generalized clonic-tonic corasol-kindled convulsions in 100% of rats but prevented kindled clonic convulsions in only 57%. This dose of sodium valproate decreased the mean severity of corasol-kindled convulsions by a factor of 1.7. Chronic enteral administration of IEM-2121, which induces combined blockade of AMPA and NMDA glutamate receptors, and IEM-1676, which blocks AMPA and NMDA receptors, as well as n-cholinoreceptors, given at doses of 10 and 20 mg/kg, respectively, had greater anticonvulsive activity than sodium valproate, as they decreased the mean severity of corasol-kindled convulsions by factors of 2.4–2.7 as compared with controls and prevented kindled clonic convulsions in 87% of rats. Combined blockade of AMPA and NMDA receptors and, possibly, n-cholinoreceptors, produced the greatest suppression of epileptogenesis in relation to both clonic and clonic-tonic corasol-kindled convulsions.

Activation of AKT/GSK3β pathway by TDZD-8 attenuates kainic acid induced neurodegeneration but not seizures in mice

Activation of glycogen synthase kinase3β (GSK3β), an enzyme that regulates a multitude of cellular signaling pathways, is implicated in neurodegenerative processes observed in an array of CNS diseases. We examined the hypothesis that the pathological changes in an acute kainic acid (KA) induced excitotoxicity model, relevant to human temporal lobe epilepsy (TLE), could be sensitive to inhibition of GSK3β by 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8) treatment in Swiss albino mice. Immediate seizure responses due to KA were recorded. Neurodegenerative and morphogenic changes were examined by western blot analysis and light microscopy, respectively, 48h after KA administration. Although tonic–clonic seizure episodes evoked by KA were unaffected, TDZD-8 pretreatment decreased KA mediated elevation in caspase-3 cleavage as well as increased Bcl2 and phospho-GSK3β (Ser9; pGSK3βSer9) expression. Likewise, microscopic examination also revealed that pretreatment with TDZD-8 attenuated cell damage elicited by KA in the CA1, CA3 and DG regions. In all the above parameters, the combined effect of a sub-effective dose of sodium valproate (SVP) with TDZD-8 was higher than that of solitary TDZD-8 treatment. The findings suggest that activated GSK3β orchestrated neurodegenerative alterations following KA treatment and its inhibition by TDZD-8 affords a distinct neuroprotective profile by activating Akt/GSK3β pathway which might act upstream of Bax/Bcl2 and caspase-3 pathways. Compounds targeting GSK3β activity might represent a novel therapeutic option for exploration as an adjunct to conventional anti-epileptic drugs in preventing neurodegenerative processes in TLE.

Low dose zinc supplementation beneficially affects seizure development in experimental seizure models in rats.

The role of zinc in seizure models and with antiepileptic drugs sodium valproate (SV) and phenytoin (PHT) was studied using experimental models of seizures in rats. Male Wistar rats, 150-250g were administered zinc 2, 20, and 200mg/kg, orally for 14days. Sixty minutes after the last dose of zinc, rats were challenged with pentylenetetrazole (PTZ, 60mg/kg, ip) or maximal electroshock (MES, 70mA, 0.2s duration). In another group, SV (150/300mg/kg, ip) or PHT (40mg/kg, ip) was administered after 30min of zinc administration followed by seizure challenge. Zinc pretreatment at all doses had no effect on MES seizures. In PTZ seizures, with the lowest dose used, i.e., 2mg/kg, a protective effect was observed. Neither the protection offered by the 100% anticonvulsant dose of SV (300mg/kg) in PTZ seizures was affected by pre-treatment with zinc nor a combination of subanticonvulsant dose of SV (150mg/kg) and zinc offer any statistically significant advantage over either drug alone. The combination of phenytoin with zinc had no effect on any of the parameters tested. Apart from this, chronic zinc administration hampered development of chemically (PTZ)-kindled seizures in rats. Zinc supplementation is unlikely to have any undesirable effect when used in epileptics rather it may offer advantage in epileptic and seizure prone patients.

Gender-Dependent Actions of the Histone Deacetylase Blocker Sodium Valproate on Olfactory Learning in 129Sv Mice during the Early Postnatal Period

The processes of histone acetylation in the brain underlie both the mechanisms supporting the long-term stable effects of early experience, transmitted to offspring generations by epigenetic inheritance, and learning. However, the role of acetylation in learning has previously been studied only in adult animals: high levels of learning can be linked with high levels of histone H3 acetylation in the brain. The role of acetylation processes in the mechanisms of early learning has not been addressed. We report here our studies of the effects of blockade of histone deacetylation with sodium valproate, which increases the level of acetylation of histone H3, on the outcome of training to olfactory discrimination in 8-day-old mice of strain 129Sv, which have low levels of learning with simulation of maternal grooming. Four doses of sodium valproate, given from day 3 to day 6 of postnatal development, were found to have gender-dependent actions: there were selective improvements in learning in males but not females, though females showed this seen after repeated administration of physiological saline. The possible epigenetic mechanisms underlying these gender-related differences are discussed.

Efficacy and safety of sodium valproate in a higher dose for treating nocturnal and early-morning seizures

Objective To explore the efficacy and safety of sodium valproate in a higher dose in the evening for treating nocturnal and early-morning seizures. Methods A total of 69 newly diagnosed pediatric patients with nocturnal or early-morning seizures were enrolled.They were randomly distributed into experimental group (35 cases) and control group (34 cases) and treated with sodium valproate tablets.The initial dose was little.It was gradually increased to the effective maintenance dose.With sodium valproate given twice a day, the post meridiem(PM) dose was twice the ante meridiem(AM) dose in the experimental group, while the PM/AM dose was equal in the control group.All patients were at least been followed up for 6 months. Results In the experimental group, 28 cases were seizure free (80.0%), and the total effective rate was 85.7%.In the control group, 20 cases were seizure free (58.8%), and the total effective rate was 64.7%.The difference in the total effective rate between the 2 groups was significant (P<0.05). No severe adverse effect was found among all patients.The incidence of daytime sleepiness (0/35 cases) in the experimental group was lower than that in the control group(2/34 cases). Conclusions A higher dose of sodium valproate in the evening for nocturnal and early-morning seizures led to better seizure control, better nocturnal sleep, less daytime somnolence, and the side effects are slight. Key words: Epilepsy; Treatment; Clinical random parallel control study; Child

Seizure With an Unusual Clinical Semiology Mimicking Psychosis: A Case Report

Seizure With an Unusual Clinical Semiology Mimicking Psychosis: A Case Report