Sodium Valproate Monotherapy Research Articles

Effect of Antiepileptic Drugs on Serum Vitamin B12 and Folic Acid Among Children with Epilepsy in Bangalore

In India, there are more than 12 million people diagnosed with epilepsy, and contributes nearly to the one sixth of global burden. Over 60% of diagnosis for epilepsy is done in childhood; hence, it is of major importance to pediatricians. we aimed to assess the levels of Vitamin B12 and Folic acid among children with epilepsy receiving antiepileptic drugs like Carbamazepine, Sodium Valproate and Levetiracetam monotherapy for >1 year. A total of 77 children with epilepsy (<18 years), on monotherapy with SV, CBZ, LEV, for minimum one year, were enrolled after obtaining consent from the parent/guardian. Children with co morbid condition like chronic kidney disease, chronic liver disease, those children who were on multiple AED’s, and children receiving treatment for <1year were excluded from the study. Out of the 77 patients, who were selected for the study, 46 were males and 31 were females. There has been a significant association between duration of treatment and Vitamin B12 and levels of Folic acid. There is also enough evidence to show that age of the patient and Folic acid levels are dependent variables. The proportion of children developing deficiency of Vitamin B12 or Folic acid after treatment with LEV is greater than the proportion treated with CBZ. The proportion of patients developing deficiency of Folic acid after treatment with LEV is greater than the same proportion after treatment with CBZ. Though there were a few significant findings as reported, we, the authors, feel that the study should be continued to ascertain if the AED’s have a significant role in Vitamin B12 and Folic acid metabolism and supplementation should be advised along with the AED’s.

Effects of sodium valproate and levetiracetam on posterior segment parameters in children with epilepsy.

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

Urinary N- acetyl - βeta -D- glucosaminidase (NAG) in children with epilepsy treated with sodium valproate monotherapy

Urinary N- acetyl - βeta -D- glucosaminidase (NAG) in children with epilepsy treated with sodium valproate monotherapy

Effects of sodium valproate monotherapy on reproductive hormonal levels in adult male epileptic patients

Aims: to assess the effects of valproate (VPA) on serum levels of testosterone, prolactin, follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol ( E2) in adult male epileptic patients in comparison to healthy controls. Methods: This study was conducted from Oct. 2005 to Aug. 2006. Patients were received from specialist neurology Clinic. Out of 62 patients interviewed only 46 fulfilled the criteria of selection . Apparently healthy 50 subjects were also included in this study as a control group. Blood samples were taken from both patients and controls and assay of testosterone, prolactin ,FSH, LH and E2 were done using radioimmunoassay (RIA) technique. Body mass index (BMI) was calculated using special equation. Results: There was a significantly higher testosterone levels in epileptic male patients on VPA therapy in comparison to healthy controls, with insignificant effect on the levels of prolactin, FSH, LH and E2. The duration of therapy and the dosage of VPA had no effect on the serum levels of the above measured parameters. Conclusion: VPA monotherapy might be associated with significant increase in serum testosterone level with insignificant effects on serum prolactin, FSH, LH and E2 in adult male epileptic patients and the duration of therapy and daily dose have no influence on such effect.

Immunoglobulins, Immunoglobulin G Subclasses and Complement C3,C4 Levels in Adult Epileptic Patients on Carbamazepine and Sodium Valproate

Objective:To assess the effects of long-term antiepileptic monotherapy (carbamazepine or sodium valproate ) on the levels of some immunological parameters ( immunoglobulins IgA, IgG, IgM , immunoglobulins G subclasses IgG1, IgG2, IgG3, IgG4 and complements C3, C4 in adult epileptic patients. Subjects and Methods: Eighty –one adult epileptic patients were included in this study , 43 on carbamazepine monotherapy and 38 on sodium valproate monotherapy , with 50 apparently healthy subjects age and sex matched taken as a control group . From both patients and control group 10 ml venous blood sample were taken and immunoglobulin serum levels (IgA, IgG, IgM) , immunoglobulin G subclass (G1, G2, G3, G4) and complement C3,C4 were assessed using kits ( Fitzgerald Industries Int. USA). Results: There was a significant reduction in IgM and IgG2 in epileptic patients on carbamazepine and a significant reduction in IgM, IgG2 and IgG4 in epileptic patients on valproate in comparison with controls. Conclusion: Carbamazepine and sodium valproate as long-term antiepileptic monotherapy have some effects on the immune-system parameters in adult epileptics.

Prognosticators of bone health in pediatrics with epilepsy using anti-epileptic drugs

Introduction: Epilepsy is a common and long-lasting neurological disorder in children who require long-term treatment with Antiepileptic drugs (AED). Such long-term AED use may have negative effects on bone causing bone loss and osteoporosis, necessitating frequent monitoring. Data on the effect of AED on bone health in children is scarce compared to adults and hence this study was undertaken. Aim: To compare and quantify the effects of sodium valproate (SV), carbamazepine (CBZ), and levetiracetam (LEV) on bone health in children using specific bone biomarkers such as vitamin D, calcium, phosphorus, ALP, osteocalcin (OCN), and beta serum cross laps (CTx). Materials and methods: A prospective interventional study was carried out in Rajarajeswari Medical College and Hospital, Bangalore, between October 2019 to March 2022. A total of 79 confirmed cases of epilepsy within the age group of 1-18 years, receiving treatment with sodium valproate (SV), carbamazepine (CBZ), and levetiracetam (LEV) monotherapy for a period of minimum one month were enrolled. Serum samples of calcium (Ca), phosphorus (PO4), alkaline phosphatase (ALP), Vitamin D were analyzed at the time of initiation of study and these levels were considered as baseline levels.

Insulin Resistance in children on Sodium Valproate - A hospital based cross-sectional study in Indian children.

Our objective was to compare the point prevalence of insulin resistance (IR) in children taking sodium valproate (VPA) and phenytoin sodium (PS) monotherapy for >1 year. 150 children, aged 6-18 years, were categorized (50 each) into - group A (VPA), group B (PS) and group C (healthy controls age-sex matched with group A). Groups were compared for metabolic complications and risk factors assessed. The point prevalence of IR and non-alcoholic fatty liver disease was significantly higher in children on VPA (12% and 34% respectively) than on PS and healthy controls, regardless of age, sex, pubertal and nutritional status. The presence of central obesity, acanthosis, hypertension, dyslipidaemia was significantly associated with IR but none showed an independent association on multivariate analysis. Therapy with VPA makes children susceptible to metabolic complications. Close monitoring will facilitate early detection and timely intervention.

UGT2B7 gene polymorphism and linkage disequilibrium in pediatric epileptic patients and their influence on sodium valproate monotherapy: A cohort study.

Background: Uridine 5′-diphospho glucuronosyl transferase (UGT) is the main enzyme responsible for the glucuronide conjugation, the principal metabolic pathway of sodium valproate. The objective of the study was to explore if there was an association between the UGT2B7 genetic polymorphism and clinical efficacy and safety in paediatric epileptic patients on sodium valproate monotherapy. Methods and materials: The cohort study included 100 pediatric epileptic patients aged 2–18 years who had been on sodium valproate monotherapy for at least 1 month. PCR-RFLP was carried out to assess the genetic polymorphism patterns of UGT2B7 (C161T, A268G, G211T). Based on the extent of seizure control throughout the 1-year follow-up, clinical outcome was assessed in terms of responders and non-responders. Hepatic, renal, and other lab parameters were assayed to determine safety. The SNPstat web software was used to calculate linkage disequilibrium. Results: Out of 100 patients, CC (38%), CT (43%), TT (19%) pattern was observed in UGT2B7 (C161T) gene, AA (15%), AG (39%), GG (46%) in (A268G) gene and GG (80%), GT (18%), TT (02%) in (G211T) gene. There was no statistical difference in clinical outcome with distinct UGT2B7 genetic polymorphism patterns, according to the findings. With low D′ and R2 values, linkage disequilibrium between alleles was statistically insignificant. However, the associations of C161T and G211T with treatment response were significant (p = 0.014) in determining treatment response. Conclusion: Our findings show that the genetic variation of UGT2B7 had no bearing on the clinical outcome of epilepsy. Gene interactions, on the other hand, had an impact on treatment response.

Effects of sodium valproate and levetiracetam monotherapy on vitamin D status in epileptic children: A study from Eastern India

The Journal is the primary organ of Continuing Paediatric Medical Education in Sri Lanka. The journal also has a website. Free full text access is available for all readers.The Sri Lanka Journal of Child Health is now indexed in SciVerse Scopus (Source Record ID 19900193609), Index Medicus for South-East Asia Region (IMSEAR), CABI (Centre for Agriculture and Bioscience International Global Health Database), DOAJ and is available in Google, as well as Google Scholar.The policies of the journal are modelled on the Committee on Publication Ethics (COPE) Guidelines on Principles of Transparency and Best Practice in Scholarly Publishing. Sri Lanka Journal of Child Health is recognised by the International Committee of Medical Journal Editors (ICMJE) as a publication following the ICMJE Recommendations.

A study of Rationale use of Sodium valproate and Levetiracetam as monotherapy in pediatric patients with Epilepsy at tertiary care hospital

Background: Drug utilization studies helps in the understanding of drug usage among patients, as well as the socioeconomic background and rational use of antiepileptics in children with epilepsy.&#x0D; &#x0D; Objective: The primary aim of this article is to examine the justification for utilizing sodium valproate and Levetiracetam as monotherapy in pediatric epilepsy patients, as well as drug use and prescribing patterns for various kinds of epilepsy.&#x0D; Materials &amp; Methods:&#x0D; Pediatric epilepsy patients under the age of 18 who visited the outpatient department, patients who were on sodium valproate, carbamazepine, or Levetiracetam monotherapy for at least 3 months after starting treatment. Demographic details, disease characteristics like type of epilepsy, onset and duration of episode, details of first attack, last attack, frequency and family history related to epilepsy comorbid conditions. Details on the treatment, such as the drug prescribed, the dose, the duration of the treatment, and the dosage, were noted. Magnetic resonance image (MRI) Brain, CT Brain, Electroencephalogram (EEG) was done in selected patients and noted. &#x0D; Results:&#x0D; In this study we have total of 91 patients younger than 18 years of age confirmed with epilepsy receiving Sodium valproate, Levetiracetam as Monotherapy. Among them 70.3% were male and 29.6% were females. As per the recent Kuppuswamy scale 64.8% of the patients were from an urban background, whereas 35.1% were from a rural background. On analyzing socioeconomic status we found that 38.5% belong to upper middle class family. Nearly 26 % of the patients were diagnosed with focal seizures and 25% with GTCS. Lesser percentage observed with Rolandic, myoclonic, complex partial, refractory epilepsy. Majority 53.8 % were on Sodium valproate among older AEDs. Among newer AEDs 29.6% of patients received Levetiracetam as monotherapy.&#x0D; Key words:&#x0D; Epilepsy, Sodium valproate, Levetiracetam, Monotherapy, Rational use&#x0D;

Serum folate levels in children on long-term anti-seizure medication in a Nigerian tertiary center-Implications for practice and public health.

Epilepsy is the most common childhood neurological disorder in Nigeria. Treatment of epilepsy is long-term and sometimes lifelong with anti-seizure medications. There are conflicting reports on the effect of anti-seizure medications on serum folate. There is therefore a need to determine the effect of a commonly used anti-seizure medication's on serum folate levels of children. This would provide an evidence-based consideration for folic acid supplementation in children on anti-seizure medication as has been suggested by some studies. To determine whether serum folate levels were lower in children taking long-term carbamazepine or sodium valproate, compared to a control group. Serum folic acid levels were measured from well-nourished children between the ages of 1-17 years on carbamazepine and sodium valproate monotherapy and their age/sex-matched controls, using spectrophotometry. The mean serum folate levels of patients on carbamazepine (43) and sodium valproate (22) were 0.032 mg/l ± 0.009 and 0.028 mg/l ± 0.008, respectively. The mean folate levels of the controls were 0.046 mg/l ± 0.03 (p = 0 001). No statistically significant difference was observed between the serum folate levels of children on the two anti-seizure medications, that is, carbamazepine and valproate. The children on treatment with carbamazepine and sodium valproate for more than 6 months had statistically significantly lower serum levels of folic acid compared to the standard reference range and controls. The serum folate levels of children on carbamazepine were not statistically different from those on sodium valproate.

Analysis of the Clinical Effects of Sodium Valproate and Levetiracetam in the Treatment of Women with Epilepsy during Pregnancy.

Objective To explore the clinical effects of sodium valproate and levetiracetam in the treatment of women with epilepsy during pregnancy. Methods The clinical data of 124 women with epilepsy during pregnancy who received monotherapy with antiepileptic drugs (AEDs) in our hospital from September 2017 to January 2020 were retrospectively analyzed. According to the type of medication taken by the patients, they were recorded as the sodium valproate group (the VPA group, n = 56) and the levetiracetam group (the LEV group, n = 68 cases). The effects and the maternal and infant outcomes after treatment were compared between the two groups. The neuron-specific enolase (NSE), cognitive function-related parameters (brain-derived neurotrophic factor (BDNF) and myelin basic protein (MBP)), and related inflammatory factors (tumor necrosis factor- (TNF-) α and interleukin- (IL-) 6) levels were compared between the two groups before and after treatment. Results After treatment, the total clinical effective rate of the LEV group was 91.18% higher than that of the VPA group 73.21%, and the frequency and duration of seizures were lower than those of the VPA group (P < 0.05). After treatment, the probability of gestational hypertension, depression during pregnancy, low-weight infants, and neonatal deformities in the LEV group was lower than that in the VPA group (P < 0.05). After treatment, the levels of NSE, MBP, TNF-α, and IL-6 in the two groups decreased, and the levels of BDNF increased, and the LEV group changed significantly compared with the VPA group (P < 0.05). Conclusion Compared with sodium valproate monotherapy, levetiracetam is more effective in controlling seizures and improving maternal and infant outcomes in women with epilepsy during pregnancy and can effectively regulate their neurological and cognitive functions and reduce the serum inflammation factor level.

Post-stroke seizures: risk factors and management after ischemic stroke.

Stroke is the leading cause of epilepsy in the elderly, ahead of degenerative diseases, tumors and head injuries. It constitutes a significant complication and a considerable comorbidity. The aim of our study was to describe the main factors implicated in the occurrence of post-stroke seizures and to identify the predictors of seizure recurrence. We conducted a descriptive, retrospective, monocentric study from January 2010 to December 2019, including patients who presented seizures following an ischemic stroke. We classified these seizures according to the International League Against Epilepsy (ILAE) into acute symptomatic seizures (ASS) if they occur within seven days of stroke, and unprovoked seizures (US) if they occur after more than one week. Clinical, para-clinical, therapeutic and follow-up data were statistically analyzed and compared. A total of 52 patients were included (39 men, 13 women; median age 55.1years). 21 cases (40%) had ASS and the remaining 31 cases (60%) presented US. Young age below 65years (71%), middle cerebral artery infarcts (83%), and cortical localization (87%) were the main factors depicted in our series. Parietal lobe infarction was more associated with US than ASS (p = 0.035). 24 patients (46%) have presented a recurrence of seizures (8/21 of ASS and 16/31 of US). The use of sodium valproate in monotherapy was identified as a recurrence risk factor (p = 0.013). In patients with post-stroke seizures, parietal lobe infarcts are more associated with US. We identified a higher risk of seizure recurrence in patients treated with sodium valproate monotherapy.

Effects of Sodium Valproate Monotherapy on Blood Liver Enzyme Levels in Patients with Epilepsy: A Meta-Analysis.

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

Association of long term sodium valproate monotherapy and vitamin D3 levels in epileptic children

Objective: To determine the association of long term sodium valproate monotherapy and vitamin D3 levels in epileptic children&#x0D; Methods: This cross-sectional study was conducted in the Department of Pediatrics, Children Hospital, Pakistan Institute of Medical Sciences, Islamabad for six months from 15th February 2019 to 14th August 2019. A total of one hundred and thirty (n=130) children and adolescents of either gender between age 3-18 years who had a history of two seizures at least 24 hours apart in their life and were on sodium valproate monotherapy for more than one year were enrolled in this study through non-probability, consecutive sampling. Serum vitamin D3 (25-hydroxy vitamin D) levels were measured in all the patients at the time of enrolment into the study. All the demographic data and laboratory investigations were entered on the predesigned proforma and analyzed through SPSS version 17.&#x0D; Results: Vitamin D3 deficiency was found in 47 (36.2%) children which were significantly higher among patients with older age and longer duration of treatment (P&lt;0.05) while gender and BMI of the patients did not show any significant difference (P&gt;0.05).&#x0D; Conclusion: Significant percentage of epileptic children on sodium valproate monotherapy was found to have vitamin D3 deficiency. Therefore we recommend routine screening of vitamin D3 deficiency in all the epileptic children on long-term sodium valproate therapy followed by vitamin D supplementation in deficient patients.&#x0D;

A COMPARATIVE STUDY ON RISK OF OSTEOPOROSIS ASSOCIATED WITH THE USE OF VALPROATE VERSUS LEVETIRACETAM IN EPILEPTIC PATIENTS AND ITS RELATIONSHIP WITH METHYLENE TETRA-HYDRO FOLATE REDUCTASE GENOTYPES

Objective: The study objects at assessing and comparing the intensity of the effect of valproate (VPA) and levetiracetam (LV) on the bone mass in young adult epileptic patients while distinguishing their methylene tetra-hydro folate reductase (MTHFR) genotypes and correlating MTHFR polymorphism and antiepileptic drugs (AEDs) usage with the risk of development of osteoporosis.&#x0D; Methods: The study design was a comparative, prospective, and observational study. It was conducted at Princess Esra Hospital (PEH), Hyderabad and genotype testing was carried out at Salar-e-Millat Research lab (PEH). The consent was obtained from total 70 subjects, divided into three groups:&#x0D; Group 1: 18 patients receiving sodium VPA monotherapy&#x0D; Group 2: 17 patients receiving LV monotherapy&#x0D; Group 3: 35 healthy control subjects from general population.&#x0D; Patients of either gender within age group of 15–40 years, experiencing generalized tonic-clonic seizures or focal seizures, receiving the AED for duration of time ≥2 years were included in the study.&#x0D; Results: Our study showed significant correlation between the AEDs treatment and MTHFR polymorphism in predisposing osteoporosis.&#x0D; Conclusion: The variants of MTHFR gene (C677T) are prone to develop increased levels of homocysteine as a result of decreased activity of the enzyme in their bodies which are further increased in patients receiving AEDs. Monitoring of homocysteine levels in epileptic patients especially in the mutants of MTHFR gene along with their periodic testing of bone mineral density levels is recommended. Treatment for low folate and calcium levels is recommended in these patients to correct their deficiencies.

UGT1A6 and UGT2B7 Gene Polymorphism and its Effect in Pediatric Epileptic Patients on Sodium Valproate Monotherapy

To evaluate the pattern of UGT1A6 and UGT2B7 gene polymorphism in pediatric epileptic patients and to compare the sodium valproate concentration in different patterns of UGT gene polymorphism. In this cross-sectional study, 99 pediatric epileptic patients aged 2-18 y receiving Sodium valproate monotherapy for the past one month were included from JusticeK S Hegde Charitable hospital, Mangalore after obtaining informed consent. Genetic polymorphism patterns were evaluated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Trough level serum valproate concentration was estimated by high-performance liquid chromatography (HPLC). Sodium valproate concentration in different UGT genotypes was compared by Analysis of Variance (ANOVA). P value <0.05 was considered significant. In the present study population, the predominant mutant allele pattern was observed in UGT1A6 (T19G, A541G, A552C) gene. In UGT2B7 (A268G, C161T) showed predominant mutant allele pattern while (G211T) showed predominant wild type. Mean steady-state sodium valproate concentration was 105.40 ± 49.9μg/ml and adjusted sodium valproate concentration was 5.5± 3.2mg/kg/L. It was found that there was no statistical difference in sodium valproate concentration in different UGT1A6 and UGT2B7 gene polymorphism. The present study concluded that though there was a difference in pattern of gene polymorphism with concerning UGT1A6 and UGT2B7, however, it has not contributed to variation in serum concentration of sodium valproate in the present study population.

Association of UGT1A6 gene polymorphism with clinical outcome in pediatric epileptic patients on sodium valproate monotherapy.

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.

Effect of UGT2B7 Gene Polymorphism with Clinical Pediatric Epileptic patients on Sodium Valproate Monotherapy

Background: Pediatric epilepsy comprises of a chronic neurological disorders characterized by recurrent seizure attack. Sodium valproate is one of the common anti-epileptic drugs used in the treatment. Glucuronide conjugation is the major metabolic pathway of sodium valproate, carried out by the enzyme Uridine 5’-diphospho (UDP) glucuronosyl transferase (UGT) whose genetic polymorphisms may alter clinical outcome. Aim: To find the association between UGT2B7 genetic polymorphism and clinical outcome in terms of efficacy and tolerability in pediatric epileptic patients on sodium valproate monotherapy. Methods and Materials: In this cohort study, 75 pediatric epileptic patients aged 2-18 years receiving sodium valproate monotherapy for past one month were included from Justice K S Hegde Charitable Hospital, Mangalore, India after obtaining informed consent. Genetic polymorphism patterns of UGT2B7 (C161T, A268G, G211T) was evaluated by PCR-RFLP. Clinical outcome was measured in terms of responders and non-responders based on seizure control during the 6 month observation period. Tolerability was measured by estimating the hepatic, renal and other lab parameters. Clinical outcome in different UGT genotypes was compared by Chi square test. P value <0.05 was considered as significant. Results: Out of 75 patients, CC (41.3%), CT (38.7%), TT (20%) pattern was observed in UGT2B7 (C161T) gene, AA(14.7%), AG(42.7%), GG(42.7%) in (A268G) gene and GG(80%), GT(18.7%), TT(1.3%) in (G211T) gene. It was found that there was no statistical difference in clinical outcome with different UGT2B7 genetic polymorphism patterns. Conclusion: We conclude from our study that genetic polymorphism of UGT2B7 doesn’t have any role on the clinical outcome of epilepsy.

Comparison of levetiracetam and sodium valproate monotherapy in childhood epilepsy-An open label randomized trial

Objectives: To compare the efficacy of oral levetiracetam and valproate in childhood epilepsy by comparing number of repeat seizures for 6 months, side effect profile, retention rates and time to first seizure. Setting-The study was conducted in tertiary care hospital of North India. Participants-Hundred children, 3-12 years of newly diagnosed epilepsy (generalised or focal motor). Intervention-Children were randomly allocated to receive oral valproate or levetiracetam in a dose of 20 mg/kg/day after initial loading dose (n=50 in each group). Drug levels were estimated by ELISA method at steady state, end of therapy and in case of any seizure activity. Side effect and repeat seizures were recorded till 6 months. Outcome measures-No repeat seizure activity for 6 months, side effect profile, achievement of therapeutic drug levels at steady state and 6 months were studied. Results: Two groups were comparable in basic demographic data. In 6 months, 8 children in valproate group and 12 in levetiracetam gr oup had r epeat seizur e (p=0.317). Mean time to first seizur e was similar in two groups (p=0.930). Mean survival time was 145.16(127.39 ± 162.93) days with levetiracetam and 159.80(145.77 ± 173.82) with valproate. The hazard ratio of valproate for treatment failure was lower. There was 38% more reduction in hazard of treatment failure with valproate compared to levetiracetam though not statistically significant (p=0.297). Overall side effects were comparable (p=0.341). Behavioural side effects were significantly more with levetiracetam (p=0.021). Conclusion: First line therapy with oral levetiracetam or valproate is comparable in efficacy and side effects in childhood epilepsy.