Antiepileptic Drug Monotherapy Research Articles

Epilepsy, Antiepileptic Drugs, and Adverse Pregnancy Outcomes, 2: Major Congenital Malformations With Antiepileptic Drug Monotherapy.

Women with epilepsy (WWE) are usually advised antiepileptic drug (AED) treatment even during pregnancy. It is therefore important to know what the major congenital malformation (MCM) risks might be with untreated epilepsy, and with first-trimester exposure to different AEDs in monotherapy. This article reviews recent findings from a large multinational registry, a large multinational population based study, and a large meta-analysis. In summary, data from the meta-analysis suggest that the MCM rate is 2%-3% in women without epilepsy and about 3% in WWE who were unexposed to AEDs during pregnancy. Data from the meta analysis also suggest that the MCM rate is approximately population level at 2.6%-3.5% with levetiracetam and lamotrigine and that it is about 4%-5% with carbamazepine, 2.8%-4.8% with oxcarbazepine, about 4% with topiramate, about 5%-7% with phenytoin, about 6%-9% with phenobarbital, and nearly 10% with valproate. The MCM risk with valproate is significantly higher than that with other AEDs (including topiramate and phenobarbital) that significantly increase the risk. Data from the registry suggest that risks are dose-dependent with valproate, phenobarbital, and carbamazepine and that the risk with valproate may be as high as 25% at doses >1,450 mg/d. Valproate is also associated with a wide range of MCMs. Data from the population-based study were generally confirmatory. Strengths and limitations of the studies are considered. The findings of these studies encourage the consideration of levetiracetam or lamotrigine monotherapy for WWE who are pregnant and strongly discourage the consideration of the older AEDs, especially phenytoin and phenobarbitone, and most especially valproate. These considerations also apply to all WWE of childbearing age because it may not be easy to change AEDs when pregnancy is planned and because pregnancy is often unplanned.

Thyroid Hormone Status in Children Taking Antiepileptic Drugs (AEDs): An Experience in a Tertiary Care Hospital of Bangladesh.

Introduction: Antiepileptic drugs (AEDs) may alter thyroid hormone homeostasis at the level of biosynthesis, release, transport, metabolism and excretion of thyroid hormones. The purpose of the study was to see the thyroid hormone status in children with epilepsy treating with common antiepileptic drugs. Materials & Method: The cross-sectional study was carried out in department of pediatric neurology, National Institute of Neurosciences and Hospital (NINS), Dhaka. One hundred and sixty epileptic children aged 1 year to 14 years who were on monotherapy or polytherapy with the most commonly used Antiepileptic drugs (AEDs) for at least 6 months or more were enrolled. Serum TSH and FT4 were measured in all selected patients with early morning serum sample. Result: Nearly one third of study subjects had thyroid dysfunction, most of which were Subclinical hypothyroidism (SCH). The frequency of SCH was 29.2% in carbamazepine(CBZ), 50% in oxcabazepine (OXC), 28.6% in phenobarbitone(PHB) and 13% in valproic acid (VPA) treated epileptic children. No child was found to have subclinical hypothyroidism with topiramate and ethosuximide monotherapy. Antiepileptic drugs (AEDs) monotherapy or polytherapy had no significant difference in alteration on thyroid hormone level. Use of CBZ for long duration significantly altered thyroid function. Doses of Antiepileptic drugs (AEDs) didn’t show any significant thyroid dysfunction. Conclusion: Commonly used Antiepileptic drugs (AEDs) in children with epilepsy were associated with alteration of thyroid hormones, most commonly subclinical hypothyroidism. BANGLADESH J CHILD HEALTH 2022; VOL 46 (2) : 58-64

The effect of anticonvulsant drugs on serum lipid profile

BACKGROUND AND OBJECTIVES: Epilepsy is a potentially life-shortening brain disorder, the symptoms of which can be successfully treated in most patients with one or more antiepileptic drug (AED). The literature explains the association of AED therapy and dyslipidemia. The changes in lipid fraction may vary with different AED, age group, and study population. The present study was planned to assess the serum lipid profile of adult epileptic patients receiving phenytoin, carbamazepine or sodium valproate therapy and attending Neurology Outpatient Department of Government Medical College, Kottayam, compared to normal healthy controls. METHODOLOGY: A total of 150 epileptic patients on AED monotherapy attending the outpatient department of neurology were evaluated for serum lipid profile. Demographic data and medical history of consenting participants were collected by the use of a semi-structured questionnaire. Fifty age- and sex-matching healthy controls also underwent similar investigation. RESULTS AND DISCUSSION: Over 12 months, 150 patients were recruited with a mean age of 35.54 ± 10.72 years (male-to-female ratio 1:1.27). When compared to normal control population observed statistically significant high mean total cholesterol, triglyceride level in the group receiving phenytoin therapy for more than 1 year. Only significant hypertriglyceridemia is observed in carbamazepine and sodium valproate treated patients. A significant correlation between the duration of anticonvulsant therapy and lipid profile was established. CONCLUSION: Conventional anticonvulsants induce dyslipidemia and monitoring of lipid profile should be done routinely to decrease the morbidity and preserve the quality of life in these (asymptomatic) patients.

PRESCRIPTION PATTERN OF ANTIEPILEPTIC DRUGS IN CHILDREN WITH EPILEPSY: A CROSS-SECTIONAL STUDY

Objective: To evaluate the pattern of prescription of antiepileptic drugs (AED) in children with epilepsy attending a tertiary care hospital in North India. Methods: An observational cross-sectional study was conducted for a duration of 1 year. Data on demographic variables including age, gender, type of epilepsy, and prescription of all AEDs and their different combinations were collected from the patients of epilepsy coming to the Department of Pediatrics, Rajindra Hospital attached to Government Medical College, Patiala, Punjab, India and analyzed using WHO core prescription indicators. Results: Out of 100 prescriptions analyzed, 55% of patients were males and 45% were females. The mean age of patients was 8.65 years (±3.80). Generalized epilepsy (78%) was the most commonly diagnosed epilepsy. 92% of patients were prescribed monotherapy, while polytherapy was used in 8% of patients. Valproate was the most common drug used in monotherapy (44.56%), followed by phenytoin (21.74%) and phenobarbitone (15.22%). In polytherapy, the most common combination used was valproate with clobazam (62.5%). 96.6% of prescriptions were based on the National List of Essential Medicines (NLEM), 2022. Conclusion: Monotherapy was the preferred modality of treatment in our hospital. Conventional drugs were favored in monotherapy, while benzodiazepines and newer drugs were more commonly used as an add-on drugs in polytherapy. Valproate was the most commonly used AED in monotherapy as well as polytherapy.

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.

Serum Level of Homocysteine, Folate, and Vitamin B12 in Adult Epileptic Patients Under Antiepileptic Therapy

Background: Epilepsy is a medical condition that requires long-term treatment with antiepileptic drugs. Different epidemiological studies revealed an increased risk of atherogenic cardiovascular diseases in patients under antiepileptic therapy. The possible etiologic suggestion is alterations of the serum homocysteine, folate, and vitamin B12 metabolism. Objective: To evaluate serum homocysteine, folate, and vitamin B12 level in patients under antiepileptic monotherapy. Methods: This cross-sectional study was conducted in the Department of Biochemistry, Dhaka Medical College from July 2017 to June 2018 through purposive sampling. In this study, forty diagnosed patients under antiepileptic monotherapy and forty age and sex-matched apparently healthy control were selected according to selection criteria, from OPD of the Neurology department, Dhaka medical college hospital. Results: In patients under antiepileptic therapy, mean (±SD) of serum homocysteine (μmol/L), folate (ng/ml), and vitamin B12 (pg/ml) were 14.15±3.4, 13.61±2.02, 361.78±41.26 respectively. In the healthy control group, serum homocysteine (μmol/L), folate (ng/ml), and vitamin B12 (pg/ml) were 8.78±2.59, 16.71±2.06 and 366.69±44.15 respectively. Serum homocysteine level was found higher and folate level was found lower in patients with antiepileptic therapy which were statistically significant (p<0.001). But serum B12 level difference was found statistically non-significant. Serum homocysteine level has a positive correlation (p-value 0.001, r value 0.71) and serum folate has a negative correlation (p-value 0.001, r value -0.65) with the duration of antiepileptic therapy. Conclusion: A higher level of serum homocysteine and a lower level of folate was found in patients under antiepileptic therapy. But there was no significant change in the serum vitamin B12 level of these patients. J Rang Med Col. March 2023; Vol. 8, No. 2:44-48

Driving performance of patients with epilepsy undergoing antiepileptic monotherapy.

Driving performance of patients with epilepsy undergoing antiepileptic monotherapy.

Primary headache types in adult epilepsy patients

BackgroundHeadache is among the most common comorbidities in epilepsy. This study examined the distribution of different primary headache disorders in a large cohort of patients with diagnosed epilepsy. Headache types were analysed with regard to gender, type of epilepsy and antiepileptic drugs (AEDs).MethodsIn this prospective single-centre study, 500 patients with epilepsy (250 female, mean age: 45.52 ± 17.26 years) were evaluated with regards to primary headache types using a validated German headache questionnaire categorizing for migraine (MIG), tension-type headache (TTH) or trigeminal autonomic cephalalgias (TAC), their combinations and unclassifiable headache. Data regarding type of epilepsy, seizure-associated headache, AED treatment and seizure freedom were collected.ResultsOf 500 patients with epilepsy, 163 (32.6%) patients (108 female and 55 male) reported suffering from headaches at least 1 day per month. MIG (without aura, with aura) and TTH were the most frequent headache type (MIG 33.1%, TTH 33.1%). Female epilepsy patients reported headaches significantly more often than male patients (x2 = 8.20, p = 0.0042). In contrast, the type of epilepsy did not significantly affect headache distribution. Of 163 patients with headache, 66 (40.5%) patients reported seizure-associated headache and AEDs were used by 157 patients. Of importance, patients with AED monotherapy suffered from MIG less often when compared to patients on polytherapy (x2 = 4.79, p = 0.028).ConclusionMIG and TTH are the most common headache types in epilepsy patients and headache is more frequent among female epilepsy patients. Monotherapy in AEDs might have a beneficial effect on the frequency of headache compared to polytherapy.

The Study of Carotid Artery Intima-Media Thickness in Children With Epilepsy on Anti-Epileptic Drugs.

Objectives. To evaluate carotid artery intima-media thickness (CIMT) and lipid profile in children with epilepsy on long-term antiepileptic drug (AED) monotherapy. Methods. We included 60 children with epilepsy receiving valproate, carbamazepine, or levetiracetam monotherapy and 60 controls. A high-resolution B-mode ultrasound was used to measure (CIMT). Measurement of serum lipids was done. Results. Patients on valproate (0.44 ± 0.03, P ≤ .001), carbamazepine (0.43 ± 0.03with P ≤ .001), and levetiracetam (0.44 ± 0.02 with P ≤ .001) monotherapy showed significantly higher CIMT compared to controls. CIMT was correlated with age (P = .041, r = .112) AEDs{valproate (P = .005, r = .731), carbamazepine (P = .038, r = .365), and levetiracetam (P = .036, r = .155)}, duration of treatment (P = .001, r = .313), TC(P = .001, r = .192), TG (P = .014, r = .018), and LDL (P = .001, r = .219). HDL (P = .003, r = -.126). Seizure severity and Apo A1 were insignificantly involved. Conclusion. Long-term monotherapy with valproate, carbamazepine, and levetiracetam in epileptic children was associated with significant abnormalities in CIMT.

Исследование когнитивных функций и речевого статуса у детей и подростков с эпилепсией на фоне противоэпилептической терапии

The effect of new-generation epilepsy drugs on the developing brain needs to be studied in detail, making a dynamic analysis of cognitive functions and speech status in children and adolescents receiving therapy extremely important. The study was conducted on a group of children aged 4 to 18 with idiopathic generalized epilepsy receiving antiepileptic monotherapy and having no cognitive disorders prior to treatment. One of the inclusion criteria was idiopathic epilepsy, which has little effect on cognitive functions. The end result was a Russian-language tool for rapid assessment of neuropsychological and speech status that neurologists, epileptologists, clinical psychologists, and linguists could use on a daily basis. The research yielded the following new findings: 1) data on new advances in genetic studies of idiopathic generalized epilepsy; 2) data on the effect of generalized epilepsy on higher mental functions, the causes of cognitive decline in patients with idiopathic generalized epilepsy, and the specifics of the development of cognitive functions in certain types of epilepsy; 3) data on changes in cognitive and speech status in children and adolescents receiving anticonvulsant monotherapy; 4) data on the frequency and types of adverse drug reactions registered in the medical records of 428 patients seen by an epileptologist in 2019–2020; 5) data on the etiology, prevalence, clinical features, and comparative effectiveness of antiepileptic drugs in the treatment of patients with juvenile myoclonic epilepsy; and 6) data on the differential diagnosis of idiopathic generalized epilepsy and type I glucose transporter deficiency syndrome (De Vivo disease).

Pharmacoeconomics Aspects of Antiepileptic Drugs in Pediatric Patients with Epilepsy

Objective: This study assessed the differentiation of treatment costs with newer and older antiepileptic drugs (AEDs) through its correlation with treatment effectiveness and an adverse event (AE) in pediatric patients with epilepsy (PPE). Methods: PPE on monotherapy of AEDs for the last 6 months were screened for this study. Seizure frequency during the study was compared with that within 6 months before the study. The following parameters were also assessed: quality of life in epilepsy, Pittsburgh Sleep Quality Index, and Liverpool AEs Profile. An incremental cost-effectiveness ratio (ICER) analysis based on the costs of pharmacotherapy was also performed. Results: Out of 80 PPE, 67 completed the study, and 13 PPE were lost after failing to meet the inclusion criteria. A total of 56.71% of PPE were on newer AEDs, and 43.28% were on older AEDs. Newer and older AEDs did not differ significantly in seizure frequency reduction and quality of life parameters, although these were improved significantly during the study period. As per ICER, newer AEDs need an additional EUR 36.82 per unit reduction in seizure frequency. Conclusion: Newer AEDs have comparatively better efficacy, although not significantly better than older AEDs. However, the additional cost per unit improvement is quite high with newer AEDs, necessitating pharmacoeconomic consideration in pediatric epilepsy treatment.

The Effects of Short- and Long-Term Therapy on Laboratory Parameters Among Pediatric Patients with Epilepsy Receiving Antiepileptic Drug Monotherapy

The Effects of Short- and Long-Term Therapy on Laboratory Parameters Among Pediatric Patients with Epilepsy Receiving Antiepileptic Drug Monotherapy

Rapid versus slow withdrawal of antiepileptic monotherapy in two-year seizure-free adults patients with epilepsy (RASLOW) study: A pragmatic multicentre, prospective, randomized, controlled study.

To establish whether a slow or a rapid withdrawal of antiepileptic monotherapy influences relapse rate in seizure-free adults with epilepsy and calculates compliance and differences in the severity of relapses, based on the occurrence of status epilepticus, seizure-related injuries, and death. This is a multicentre, prospective, randomized, open label, non-inferiority trial in people aged 16 + years who were seizure-free for more than 2years. Patients were randomized to slow withdrawal (160days) or rapid withdrawal (60days) and were followed for 12months. The primary outcome was the probability of a first seizure relapse within the 12-months follow-up. The secondary outcomes included the cumulative probability of relapse at 3, 6, 9, and 12months. A non-inferiority analysis was performed with non-inferiority margin of - 0.15 for the difference between the probabilities of seizure recurrence in slow versus rapid withdrawal. The sample comprised 48 patients, 25 randomized to slow withdrawal and 23 to rapid withdrawal. Median follow-up was 11.9months. In the intention-to-treat population, 3 patients in the slow-withdrawal group and 1 in the rapid withdrawal group experienced seizure relapses. The corresponding probabilities of seizure recurrence were 0.12 for slow withdrawal and 0.04 for rapid withdrawal, giving a difference of 0.08 (95% CI - 0.12; 0.27), which is entirely above the non-inferiority margin. No patients developed status epilepticus and seizure-related injuries or died. Risks were similar in the Per-Protocol population. Seizure-relapse rate after drug discontinuation is lower than in other reports, without complications and unrelated to the duration of tapering.

Evaluation of one-year effectiveness of clobazam as an add-on therapy to anticonvulsant monotherapy in participants with epilepsy having uncontrolled seizure episodes: An Indian experience

ObjectivesTo prospectively study the effectiveness and safety of clobazam as an add-on therapy in patients with epilepsy whose seizures are not adequately controlled with antiseizure medicine (ASM) monotherapy. MethodsWe conducted a prospective, observational study at 28 neurology outpatient clinics in India from June 2017 to October 2019. Consecutive patients with epilepsy (older than 3 years) with inadequate seizure control with ASM monotherapy were initiated on clobazam. Patients were followed up at 1, 3, 6, 9, and 12 months. Seizure control and adverse events were assessed through personal interviews and seizure diaries. ResultsOut of 475 eligible patients, data of 429 patients (men: 65.5%) were evaluated (46 excluded due to protocol deviations). The median age was 25 (range, 3–80 years) years and the median duration of epilepsy was 3 (0.1–30) years. The majority of patients had focal epilepsy (55.0%) and genetic generalized epilepsy (40.1%). The one-year follow-up was completed by 380 (88.5%) patients. At one-year follow-up, 317 (83.4%; N = 380) patients in the study remained seizure free. These 317 patients who were seizure free at 12 months comprised 73.9% of the evaluable population (N = 429). In 98.8% of patients, the primary reason for adding clobazam was inadequate control of seizures with treatment. During one-year follow-up, a total of 113 (22.6%) patients experienced at least one adverse event which included 103 (20.6%) patients who experienced 386 episodes of seizures. ConclusionThe study provides preliminary evidence that clobazam is effective and well-tolerated as add-on therapy for a period of one year among patients with epilepsy inadequately stabilized with monotherapy. Trial registration numberCTRI/2017/12/010906.

Demographic Profile and Prescribing Patterns of Anti-epileptic Drugs in Indian Epilepsy Patients: Electronic Medical Record-Based Nation-Wide Retrospective Cohort Study.

The aim of this study was to provide real-world data on clinical characteristics, risk factors, and treatment patterns in Indian patients with epilepsy. Electronic medical record (EMR) data of patients diagnosed with epilepsy between January 2001 and December 2019, which included demographics, diagnosis, anti-epileptic drug usage, and underlying risk factors were evaluated. The majority of patients were between the age group of 18 and 55 years (n=3,186), with males accounting for 62% and the remaining 38% being females. Further, the most common comorbidity was hypertension (23.3%, n=1,470), followed by diabetes mellitus (10.8%, n=683) and depression (9.4%, n=597). The most prevalent form of epilepsy was focal epilepsy (n=5,141 81.4%), followed by generalized epilepsy (n=601). Focal epilepsy was most prevalent in males (62%, n=3,167) and most common in the age group of 18-55 years (50.3%, n=2588). Anti-epileptic drug (AED) usage data from 6,318 patients showed that the most commonly prescribed AED alone or in combination for both focal and generalized epilepsy was levetiracetam (41.8%, n= 2645). Data collected from this study are aligned but do not completely agree with the Guidelines for the Management of Epilepsy in India (GEMIND). This affirms treatment initiation with AED monotherapy; however, the treatment choices do not necessarily follow the recommended guidelines to select conventional AEDs, at low strengths, at initiation.

Adverse drug reaction of antiepileptic monotherapy on epileptic paediatric patients in Dr Sardjito Hospital, Yogyakarta, Indonesia

Introduction: Epilepsy is a neurological disease with the highest prevalence in paediatrics. Using anti-epileptic drug as monotherapy is the first-line therapy for paediatrics based on risk-benefit ratio consideration in the patients effectiveness and adverse drug reaction of anti-epileptic monotherapy drug for the cognitive function in paediatric patients. Objectives: The aim of the study is to assess effectivity and adverse drug reaction of anti-epileptic monotherapy drug for the cognitive function in paediatric patients. Methods: This was a cross sectional study. This study used patients from the Dr. Sardjito hospital’s outpatient paediatric unit’s Neurology division from May to July 2013 and May to June 2019 to select the subjects. Patient questionnaires and medical records provided the data that was used. Effectiveness was assessed by seizure severity with Hague Seizure Severity Scale (HASSS) questionnaire and seizure frequency, while adverse drug reactions in cognitive function were assessed by the PESQ (Pediatric Epilepsy Side Effect Questionnaire) instrument. Results: In total, 29 patients received monotherapy, with 26 patients (89.66%) receiving valproate, two (6.89%) receiving phenytoin, and one (3.45%) receiving phenobarbital. A total 89.66% of patients did not have severe seizures, but 6.90% had moderate seizures. The cognitive function of epileptic patients with co-morbidities receiving valproate monotherapy had moderate (27.59%) and severe (20.69%) side effects. The adverse drug reaction experienced in epileptic patients without co-morbidities using valproate was with the cognitive function, with 6.89% of patients experiencing severe effects, 13.79% moderate and 20.69% mild effects. Conclusion: While anti-epileptic monotherapy can control seizures in children, the commonly prescribed valproate can impair cognitive function, especially in those with co-morbidities.

The perspectives of pharmacological correction of depressive disorders and cognitive deficit as post-traumatic epilepsy leading syndromes

Traumatic brain injury is the leading cause of symptomatic epilepsy at a young age. Post-traumatic epilepsy (PTE) is the main factor in disabling patients of working age and impairs the quality of life. Comorbid pathology in the form of psychoemotional and cognitive disorders essentially has a single pathogenetic mechanism on the part of traumatic brain disease. There are problems with differential diagnosis between comorbid and direct manifestations of PTE. The above dictates the need to develop modern complex approaches to the treatment of PTE and correction of accompanying and comorbid pathological conditions. Author tries to develop new pathogenetically adequate approaches to the treatment of PTE with correction of the psycho-emotional sphere and cognitive deficit. 44 patients with PTE were examined. The average period of its formation reached 10.3±4.2 years, and the frequency of attacks – 2.4±0.9 per month. Focal attacks prevailed (61.4%). In addition to standard long-term anticonvulsant monotherapy, the main group (32 patients) was prescribed ethylmethylhydroxyperidine succinate and vortioxetine. The control group (12 patients) received only anticonvulsant therapy.
 When using the proposed complex treatment, the number of people with depression decreased from 25 (56.8%) to 10 (22.7%) cases, that is, by 2.5 times (P <0.05). In the main group, from 59.4% to 21.9%, i.e. 2.7 times (Р<0.05). In the control – from 50.0% to 41.7% (Р>0.05). 37.5% registered positive dynamics in relation to pathological activity on the electroencephalogram. According to the Luria A. R. test, the average values of the obtained data at all stages of word presentation were probably higher than at the beginning of the study. Indicators of long-term memory changed similarly.
 Thus, the proposed treatment approach has a beneficial effect on the main pathogenetic links of the development of PTE, its course and corrects cognitive deficits, psychoemotional layers, which are comorbid conditions.

Neuropsychological effects in children exposed to anticonvulsant monotherapy during gestation: Phenobarbital, carbamazepine, and phenytoin

ObjectiveUsage during pregnancy of the antiseizure medication (ASM), phenobarbital (PB), carbamazepine (CBZ), and phenytoin (PHT), has been associated with adverse pregnancy outcomes. While morphological effects on offspring are well-documented, inconsistent findings have been reported on neuropsychological development, possibly due to differences in attention to maternal demographics, and other design characteristics. Herein, we report the results of a carefully designed protocol used to examine the effects of gestational monotherapy with PB, CBZ, or PHT upon children’s general mental abilities, when compared to age- and gender- matched children born to unexposed women of similar age, education, and socioeconomic status. MethodsFor each ASM, we selected qualifying cases from children born to PB, CBZ, or PHT monotherapy-exposed and unexposed women. Following the application of inclusion, exclusion, and matching criteria, our sample included 34 PB-exposed, 40 PHT-exposed, and 41 CBZ-exposed children along with matched unexposed children for each drug group. Criteria were applied through examination of maternal medical and educational histories, parental socioeconomic characteristics, and child’s age and gender. Each child’s physical and neuropsychological characteristics were examined, using standardized protocols. We report on the cognitive performance of the children as assessed by the Wechsler Intelligence Scale for Children – III (WISC-III), the leading measure of mental ability in the U.S. ResultsAn overall mixed model ANOVA of the adjusted performance of the children across all groups controlling for maternal IQ revealed significant effects on verbal IQ, but not full-scale IQ or performance IQ. In the individual drug and unexposed group comparisons, only reduced verbal and full-scale IQ scores in PB-exposed versus matched unexposed children were found. Comparisons between drug groups revealed a significant reduction in verbal IQ and full-scale IQ in PB-exposed versus PHT-exposed children, but not in other drug–drug comparisons. SignificanceThese results demonstrate effects on children’s mental ability due to prenatal PB exposure, such that analyses adjusted for maternal IQ scores, revealed reduced verbal mental abilities and reduced full-scale IQ scores when scores in exposed children were compared to scores from children of the same age and sex born to demographically similar, healthy unexposed women. When comparisons were made between drug groups, children exposed prenatally to PB performed significantly worse than prenatally PHT-exposed children, but CBZ-exposed children’s scores were not significantly different from those of PB or PHT-exposed groups. In light of shared effects on structural teratogenicity, these findings suggest that use of PB monotherapy for the management of seizures during pregnancy may be associated with increased risk in comparison to PHT when neurobehavioral functioning is considered, and that only PB-exposed children have reduced performance compared to matched controls. Attention to these effects is critical in the developing world where use of these older medications remains predominant, and prudent choices can be made to reduce impact on cognitive development.

Prevalence of vitamin D insufficiency and deficiency among children with epilepsy

Background and aim The relation between vitamin D, the use of antiepileptic drugs (AEDs), and bone integrity has been found in patients with epilepsy. The aim of the work was to study the prevalence of vitamin D insufficiency and deficiency among children with epilepsy, and to identify some possible risk factors. Patients and methods A comparative cross-sectional study was done on randomly chosen 60 children with epilepsy aged 3–15 years attending the neurology out-patient clinic and 20 healthy age-matched and sex-matched children, attending the pediatric outpatient clinic at Alexandria University Children’s Hospital from September 2014 to March 2015. They were divided into three groups: group I included 40 children receiving AED monotherapy for more than 1 year; group II included newly diagnosed epileptic children before receiving medications; group III included 20 healthy children as controls. History taking included patients’ age, sex, seizure history, nutritional history, sunlight exposure, associated illness or drug intake and history of vitamin D or calcium supplementation. Clinical examinations were done (systematic and neurological examination, weight and BMI). Laboratory investigations [liver and kidney function tests, serum calcium, phosphorus, alkaline phosphatase, and serum 25-hydroxyvitamin D (25(OH)D) levels] were done. Electroencephalogram was done for groups I and II. Results There was no significant difference between all groups regarding age and sex. The BMI was significantly different between groups II and III. Laboratory tests (alanine aminotransferase, aspartate aminotransferase, urea, creatinine, serum calcium, phosphorus, and alkaline phosphatase levels) showed no significant differences between the three studied groups. The mean of 25(OH)D among children in group I was significantly lower compared with children in group III. Females were associated with insufficient and deficient levels of vitamin D. There were statistically significant relations between 25(OH)D levels and BMI and the duration of AED treatment in group I. Conclusion The present study provides evidence of the increased prevalence of vitamin D insufficiency and deficiency among newly diagnosed children with epilepsy and in those on treatment with AEDs. In addition, the study has indicated that female sex, high BMI, AED use (carbamazepine, Na valproate) and prolonged duration of treatment are risk factors for vitamin D insufficiency and deficiency.

Antiepileptic-drug tapering and seizure recurrence: Correlation with serum drug levels and biomarkers in persons with epilepsy.

OBJECTIVES:Antiepileptic-drug (AED) serum level and inflammatory biomarkers are primarily monitored/assessed during epilepsy treatment for effective seizure control; however, their correlation with seizure recurrence (SR) following AED-tapering has not been established, and this is being investigated in this study.MATERIALS AND METHODS:This prospective observational study enrolled persons with epilepsy (PWE) on AED monotherapy and going to start tapering after being seizure-free for ≥2 years. Data regarding seizure episodes, AED-treatment, and adverse events (using Liverpool Adverse Event profile [LAEP]-score) were recorded. Serum AED levels using high-performance liquid chromatography and biomarkers levels through enzyme-linked immunosorbent assay kits were estimated at AED-tapering commencement and at 6 months/SR time.RESULTS:Among 129 enrolled PWE (levetiracetam [n = 52], valproate [n = 34], carbamazepine [n = 29], and phenytoin [n = 14]), SR occurred in 23.3% during follow-up (range 12–44 months). PWE with subtherapeutic serum AED level at the onset of tapering had higher SR (P = 0.004) than those with therapeutic or higher levels. Levetiracetam-treated PWEs with SR have significantly low AED levels than PWE with no-SR (P < 0.001). PWE had significantly raised inflammatory biomarkers (interleukin [IL]-1 β, tumor necrosis factor [TNF]-α, IL-6, and high-mobility group box protein 1) and decreased IL-10 than healthy control subjects. SR and no-SR groups did not differ significantly in inflammatory markers except for higher IL-1 β and TNF-α levels in SR group (P = 0.001, 0.02, respectively). Improvement in LAEP score was observed in follow-up visits without any difference between SR and no-SR groups.CONCLUSION:Low serum AED levels (especially levetiracetam) and raised levels of TNF-α and IL-1 β during tapering commencement had a higher association with SR following AED-tapering.