Background and PurposeThere is sparsity of quality evidence for the use of drugs after first-line benzodiazepines in convulsive status epilepticus in children. The aim of the study was to compare the clinical efficacy and safety of intravenous levetiracetam versus intravenous phenytoin as second-line drugs in the management of generalized convulsive status epilepticus in children.MethodsThis open-label randomized controlled trial was conducted in the Emergency Department of The Children's Hospital and The Institute of Child Health, Multan, Pakistan over a period of 4 years and 6 months from January 2014 to June 2018. This study included 600 children with generalized convulsive status epilepticus: 300 in the 40 mg/kg levetiracetam group, and 300 in the 20 mg/kg phenytoin group. Cessation of a clinical seizure (seizure cessation rate) within 30 minutes after the end of drug administration was the primary outcome in this study, and the presence or absence of adverse effects was noted as the secondary outcome. Data were analyzed using SPSS (version 20.0).ResultsThe children in the levetiracetam and phenytoin were aged 3.5±0.2 and 3.4±0.2 years (mean±SD), respectively, their seizure durations before the start of treatment were 25.1±0.6 and 23.8±0.4 minutes, and their treatment efficacies were 278/300 (92.7%) and 259/300 (83.3%). Levetiracetam was significantly more effective than phenytoin (p=0.012), with no significant difference in safety. Adverse events were observed in eight children in the phenytoin group.ConclusionsLevetiracetam is significantly more effective than phenytoin for the treatment of convulsive status epilepticus in children who have failed to respond to benzodiazepines.
Background Intellectual disability (ID) is both a clinically diverse and genetically heterogeneous group of disorder, with an onset of cognitive impairment before the age of 18 years. ID is characterized by significant limitations in intellectual functioning and adaptive behaviour. The identification of genetic variants causing ID and neurodevelopmental disorders using whole-exome sequencing (WES) has proven to be successful. So far more than 1222 primary and 1127 candidate genes are associated with ID. Methods To determine pathogenic variants causative of ID in three unrelated consanguineous Pakistani families, we used a combination of WES, homozygosity-by-descent mapping, de-deoxy sequencing and bioinformatics analysis. Results Rare pathogenic single nucleotide variants identified by WES which passed our filtering strategy were confirmed by traditional Sanger sequencing and segregation analysis. Novel and deleterious variants in VPS53, GLB1, and MLC1, genes previously associated with variable neurodevelopmental anomalies, were found to segregate with the disease in the three families. Conclusions This study expands our knowledge on the molecular basis of ID as well as the clinical heterogeneity associated to different rare genetic causes of neurodevelopmental disorders. This genetic study could also provide additional knowledge to help genetic assessment as well as clinical and social management of ID in Pakistani families.
Epilepsy is a heterogeneous disorder and its treatment is often complicated by variable drug response. Antiepileptic properties of Valproic acid were discovered in 1963 and since then it is widely used for treatment of epilepsy. The objective of this study was to explore the correlation of steady state serum level of Valproic acid with dose, seizure response and frequency of adverse drug reactions in Pakistani children with epilepsy. This prospective analytical study was conducted in the Neurology Department-The Children Hospital and The Institute of Child Health Multan, Pakistan from March 2009 to February 2010. Sixty children between one to 14 years of age taking Valproic acid for treatment of epilepsy, for more than 3 months as monotherapy were included. Age, sex, dose of Valproic acid, type of seizure, response of seizure with treatment and any side effect of drug were noted. Trough Valproic acid serum level was measured by Latex Enhanced Immunoturbidometric Method by Randox VPA 1?Series Kit according to manufacturer instructions. Chi square test was used to measure the relationship of serum level with dose, seizure response and frequency of adverse drug reactions. P value of less than 0.05 was considered as significant. Our results showed that male female ratio was 1.1:1. Mean age was 7.3 ? 3.9 yr. Mean dose of Valproic acid was 32.4 ? 11.3 mg/kg/day. Generalized tonic clonic seizures were noted in 50% of patients, complex partial in 16.7%, myoclonic in 15%, absence seizures in 5% and mixed type of seizures was noted in 8.3% of patients. Complete seizure response was noted in 60% of patients, partial response in 18.3% and no response in 21.7% of patients. Serum level of 50?100 ?g/mL (therapeutic) was noted in 38.30% of patients, below 50 ?g/mL (subtherapeutic) in 46.8% and above 100 ?g/mL (supratherapeutic) in 14.9% of patients. Serum level below 50 ?g/mL was noted in 60.7% of children with complete seizure response while 50?100 ?g/mL was noted in 21.7% of children with no response. Adverse drug reactions were noted in 66.6% of patients in this study. These adverse reactions were noted in 64.2% of children with serum level below 50 ?g/mL, 65.2% with 50?100 ?g/mL and 77.7% with serum level above 100 ?g/mL. No correlation of Valproic acid serum level was noted with dose (P value 0.546), seizure response (P value 0.998) and frequency of adverse drug reactions (P value 0.743) in this study. No significant correlation of Valproic acid serum level was noted with dose, seizure response and frequency of majority of adverse drug reactions.
Objective: To assess efficacy and safety of Levetiracetam (LEV) as add-on therapy in children with refractory seizure. Methodology: This prospective observational cohort study was conducted in the Outpatient Department of Paediatric Neurology, “The Children’s Hospital & Institute of Child Health, Multan”, Pakistan from 15th January 2020 to 14th January 2021. Fifty children of aged 2 months to 14 years of both genders with refractory epilepsy were enrolled and received oral LEV. Data on LEV efficacy and side effects were recorded. The medication was considered as “effective” when all seizures had ceased within 3 months, “partially effective” when seizure frequency was decreased by ≥50% and “ineffective” when seizure frequency was decreased by < 50%.or seizure frequency remain unchanged during a period of 3 month. Results: Out of a total of 50 participants, there were 35 (70.0%) male. Mean age was 4.81±3.79 years while mean age at onset of seizures was 2.51±2.85 years. Most frequent type of seizures was generalized tonic clonic seizures in 19 (38.0%) patients followed by focal clonic seizures in 13 (26.0%) patients. Levetiracetam was effective in 14 (28%) patients, partially effective in 24 (48.0%) and not effective in 12 (24.0%) patients. Conclusion: Levetiracetam as add-on therapy reduced the seizure frequency in 76% of the participants without any significant side effects. Keywords: Levetiracetam, refractory seizure, epilepsy, add-on therapy, efficacy.
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