Antiepileptic Drug Monotherapy Research Articles

Profile of People with Epilepsy seen at a Tertiary Hospital in North-West Nigeria

Epilepsy is one of the most prevalent chronic non-communicable neurological disorder. Persons with epilepsy (PWE) have unique characteristics that have social impacts on the affected individuals and their family. This study sought to describe the profile of patients with epilepsy attending the out-patient neurology clinic in a tertiary health care centre in North West Nigeria. The study was carried out at Neurology clinic of Ahmadu Bello University Teaching Hospital Kaduna State, Nigeria from August 2013 to October 2014. Consecutively presenting PWE on follow-up were recruited after obtaining ethical approval and informed consent. Those recruited were at least 18 years and have been on routine follow-up for at least 1 year. Patients with clinical and electroencephalography (EEG) features suggestive of non-epileptic seizures, acute metabolic or febrile illness precipitating seizures were excluded. A structured questionnaire was used to obtain all relevant information. The data was analyzed using SPSS version 17 with p-value set at less than 0.05. A total of 103 PWE were recruited with median age of 29 years. More than 50% were in the 21-30 years age group. About 55.3% were single (never married), 58.2% were unemployed and earned < ₦50,000.00 monthly income. The median age of onset of epilepsy was 20 years, while median duration of illness was 7 years. About 50.5% were focal seizures, with traumatic head injury (14.6%) and febrile convulsion (12.6%) as aetiological factors, while 52.5% of them had no identifiable aetiological factor. About 96% were on antiepileptic drug monotherapy, 82% of them on carbamazepine only for a median duration of 7.5 years. Our study shows that epilepsy is predominant among the young population, who are mostly single (never married), unemployed, with poor monthly income occurring more as focal seizure type, with majority of them on carbamazepine monotherapy. There is the need for public enlightenment campaign and effort targeted at mitigating the prevalence of the disease among the young and productive population.

Treatments for Convulsive and Nonconvulsive Status Epilepticus in Adults: An Expert Opinion Survey in South Korea.

Background and PurposeThe aim of this study was to survey the expert opinions on treatments for convulsive status epilepticus (CSE) and nonconvulsive status epilepticus (NCSE) in adults.MethodsForty-two South Korean epileptologists participated in this survey. They completed an online questionnaire regarding various patient scenarios and evaluated the appropriateness of medications used to treat CSE and NCSE.ResultsInitial treatment with a benzodiazepine (BZD) followed by either a second BZD or an antiepileptic drug (AED) monotherapy was the preferred treatment strategy. More than two-thirds of the experts used a second BZD when the first one failed, and consensus was reached for 84.8% of the survey items. The preferred BZD was intravenous (IV) lorazepam for the initial treatment of status epilepticus. IV fosphenytoin and IV levetiracetam were chosen for AED monotherapy after the failure of BZD. The treatments for NCSE were similar to those for CSE. Continuous IV midazolam infusion was the treatment of choice for iatrogenic coma in refractory CSE, but other AEDs were preferred over iatrogenic coma in refractory NCSE.ConclusionsThe results of this survey are consistent with previous guidelines, and can be cautiously applied in clinical practice when treating patients with CSE or NCSE.

NCMP-08. EFFICACY OF ANTIEPILEPTIC DRUGS IN GLIOMA PATIENTS WITH EPILEPSY: A SYSTEMATIC REVIEW

Abstract BACKGROUND Epilepsy is a common symptom in glioma patients, requiring antiepileptic drug (AED) treatment. However, comprehensive data on the efficacy and tolerability of AED treatment is currently lacking. In this systematic review we specifically assessed the efficacy of AEDs in patients with a grade II-IV glioma. METHODS Electronic databases PubMed/MEDLINE, EMBASE, Web of Science, and Cochrane library were searched up to April 2020. Three different outcomes were extracted from all eligible articles: (I) seizure freedom; (II) ≥50% reduction in seizure frequency; and (III) treatment failure. To overcome variation with respect to sample sizes, weighted averages (WA) were calculated for outcomes at 6 and 12 months. RESULT A total of 64 studies were included. For monotherapy, the 6-months seizure freedom rate was highest for phenytoin (WA=72%), whereas the 12-months seizure freedom rate was highest for pregabalin (WA=75%). For achieving ≥ 50% seizure reduction, levetiracetam was the most effective AED at 6 and 12 months, with WA of 82 and 97% respectively. Considering the provided polytherapy combinations, levetiracetam combined with phenytoin was most effective followed by levetiracetam with valproic acid. Seizure freedom rates with polytherapy at 6 months and 12 months were highest for combinations with phenytoin and topiramate, respectively. For achieving a ≥ 50% seizure reduction, combinations with perampanel were found to be the most effective at 6 and 12 months. CONCLUSION Based on the current literature, phenytoin, levetiracetam and pregabalin are most effective as AED monotherapy in glioma patients with epilepsy. Well-controlled prospective studies are needed to help further guide clinician’s treatment choices.

Ictal ECG changes and antiepileptic drug therapy

Abstract Purpose Epileptic seizures may cause severe cardiac arrhythmias. Most people with epilepsy die suddenly and whose death is recognized to a sudden unexpected death in epilepsy (SUDEP). There are controversial reports on the association between polytherapy using antiepileptic drugs and SUDEP. First-line drugs include, in particular, carbamazepine, oxcarbazepine, and lamotrigine, which are sodium channel blockers that may impair heart function. Often a patient requires a combination of antiepileptic drugs Methods 204 patients with epilepsy and were on antiepileptic drugs therapy. The ECG cardiac monitor was implanted in all patients (n=204) and was analyzed together with the preclinical data including age, sex, family history, cardiac risk factors (hypertension, dyslipidemia, diabetes mellitus), heart disease, antiepileptic drug type. Results After a follow-up of 12-month ictal ECG changes (rhythm and conduction disturbances, ST segment abnormalities) were observed in 134 (66%) patients, and only in 70 (34%) – without ictal ECG changes, the average age in these groups was 34,4±9,9 and 36,7±11,8 years (p>0,05). In the group with ictal ECG changes among patients receiving as monotherapy antiepileptic drugs, ictal ECG changes were found in 53.7% of cases, with polytherapy antiepileptic drugs significantly more often – in 71.5% of cases (p<0.05). a reliable association between carbamazepine and changes in sinoatrial and atrioventricular conduction (p=0.01) was significant. In the analyzed group of patients, carbamazepine therapy was also associated with the presence of ictal ST-segment abnormalities (depression/elevation) (p=0.013). A positive association was observed between the administration of oxcarbazepine and development of ictal tachycardia (p=0.04) and ictal right and left bundle branch block, which was observed in 71.4% of cases against the background of oxcarbazepine, significantly more often than with other drugs (p=0.005). Conclusion In agreement with previous publications available in the literature, our results confirm the risk of high-frequency rhythm and conduction disturbances, ST segment abnormalities related to antiepileptic drugs, in particular, carbamazepine and oxcarbazepine and indicates the need of not only cardiological examination before prescribing an antiepileptic drugs, but also a thorough follow-up during the therapy. Patients with ictal ECG changes, primarily rhythm and conduction disturbances, should be under the dynamic control of not only neurologists but also cardiologists and require regular cardiological check-up (ECG, Holter monitoring of the electrocardiogram, echocardiography). Funding Acknowledgement Type of funding source: None

Risk of early neurodevelopmental disorders associated with in utero exposure to valproate and other antiepileptic drugs: a nationwide cohort study in France

Information available on the risks of neurodevelopmental disorders (NDs) associated with in utero exposure to valproate (VPA) and to other antiepileptic drugs (AEDs) is limited. A nationwide population-based cohort study was conducted based on comprehensive data of the French National Health Data System (SNDS). Liveborn infants without brain malformation, born between January 2011 and December 2014, were followed from birth up to December 2016. NDs were identified based on diagnoses of mental or behavioural disorders and utilization of speech therapy, orthoptic or psychiatric services. The risk of NDs was compared between children exposed in utero to AED monotherapy and unexposed children, using Cox proportional hazard models adjusted for maternal and neonatal characteristics. The cohort included 1,721,990 children, 8848 of whom were exposed in utero to AED monotherapy. During a mean follow-up of 3.6 years, 15,458 children had a diagnosis of mental or behavioural disorder. In utero exposure to VPA was associated with an increased risk of NDs overall (aHR: 3.7; 95% CI 2.8–4.9) and among children born to a mother without mental illness (aHR 5.1; 95% CI 3.6–7.3). A dose–response relationship was demonstrated and the risk of NDs was more particularly increased for an exposure to VPA during the second or third trimesters of pregnancy. Among the other AEDs, only pregabalin was consistently associated with an increased risk of NDs (aHR: 1.5; 95% CI 1.0–2.1). This study confirms a four to fivefold increased risk of early NDs associated with exposure to VPA during pregnancy. The risk associated with other AEDs appears much lower.

Enduring language deficits in children of women with epilepsy and the potential role of intrauterine exposure to antiepileptic drugs.

Exposure to certain intrauterine antiepileptic drugs (AEDs) can negatively influence the language skills and intelligence of young children. It remains unanswered whether these deficits are transient or persist as children grow up. This study aims to evaluate the language function of children of women with epilepsy (CWE) aged 9-13years in comparison with their peers, and its relationship with intrauterine AED exposure. We included 191 CWE in our study from the Kerala Registry of Epilepsy and Pregnancy. Children in the same age group (n=144) and without maternal epilepsy or antenatal AED exposure served as controls. We used Clinical Examination for Language Function version IV to assess language in both groups. Relevant data related to maternal epilepsy and AED use were obtained from the registry records. The average Core Language Scaled Score (CLSS) was significantly lower in CWE as compared to controls (83.19 vs 90.18, P=.001). Similarly, the mean scaled scores in other language parameters were also significantly lower in CWE. In the multivariate analysis, compared to control children, the average CLSS in CWE was 4.5 units lower (95% confidence interval [CI] = -8.8 to -0.2, P=.04) with AED monotherapy exposure and 7.3 units lower with exposure to AED polytherapy (95% CI = -13.8 to -0.8, P=.03). Intrauterine exposure to phenobarbitone (n=61) and valproate (n=55) as either monotherapy or polytherapy showed a negative effect on CLSS in CWE as compared to control children. However, carbamazepine (n=75) and phenytoin (n=37) use was not associated with significant variation of CLSS. In head-to-head comparisons between AED monotherapies in CWE, phenobarbitone showed a negative effect on CLSS (-14.7, 95% CI = -23.1 to -6.4, P=.001) as compared to carbamazepine. Intrauterine exposure to phenobarbitone and valproate impairs language development in CWE, with effects persisting into the second decade.

Need for pharmacoeconomic consideration of antiepileptic drugs monotherapy treatment in persons with epilepsy

ObjectiveNewer antiepileptic drugs (AEDs) are expected to have less adverse effects (AEs) and drug interactions as compared to conventional AEDs but the high cost is the major limitation for their use. This study evaluated variation in the cost of treatment with newer and conventional AEDs through its correlation with treatment efficacy and AEs in persons with epilepsy (PWE). MethodsThis cross-sectional study included PWE (28.9 ± 9.9 years) having focal and generalized seizures on conventional [valproate, carbamazepine, phenytoin] or newer AEDs [levetiracetam, oxcarbazepine] for >6 months. Seizure frequency during the study (6 months) was compared to that within 6 months before the study. Other parameters assessed were Quality of life in epilepsy, Pittsburgh Sleep Quality Index, Gastrointestinal Quality of life Index, and Liverpool AEs Profile. The cost of treatment was determined as direct, indirect, and intangible costs. The incremental cost-effectiveness ratio (ICER) analysis was also performed. ResultsOut of 214 PWE, 51.4% were on newer AEDs. Newer and conventional AEDs did not differ significantly in seizure frequency reduction (60.29 vs. 53.09%), quality of life parameters, though these were improved significantly during the study period. The direct medical cost and total cost of treatment were lesser with conventional AEDs (p < 0.001 in both) than newer AEDs, but the intangible cost did not differ. The total cost of treatment was significantly influenced by factors (as per regression analysis) including the type of AEDs (significant difference between valproate, carbamazepine, and levetiracetam), frequency of seizures, cost of medicine (70.34% of total cost), hospital admission, and treatment of AEs. As per ICER, newer AEDs need an additional USD 8.39 per unit reduction in seizure frequency. ConclusionNewer AEDs have comparatively better efficacy, though not significant than conventional AEDs. However, the additional cost per unit improvement is quite high with newer AEDs, necessitating pharmacoeconomic consideration in epilepsy treatment.

Antiepileptic combination therapy with Stevens-Johnson syndrome and toxic epidermal necrolysis: Analysis of a Japanese pharmacovigilance database.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are immune-mediated diseases characterized by an extensive loss of the epidermal skin layer, often resulting in death. SJS and TEN are often triggered by certain drugs, including antiepileptic drugs (AEDs). Epilepsy is very difficult to treat and often involves the combination of two or more AEDs. In this study, we quantified not only the risk of SJS or TEN associated with single-AED therapy but also the risk related to concomitant AED treatment using reporting-derived signals. An analysis of the Japanese Adverse Drug Event Report (JADER) database was performed from the first quarter of 2004 to the fourth quarter of 2018. The single-AED signals were evaluated using the proportional reporting ratio (PRR), and the combination therapy signals were evaluated using Ω shrinkage measure and combination risk ratio (CRR). SJS signals were associated with 11 AEDs, and TEN signals were related to 12 AEDs. Moreover, the following AED combinations were associated with SJS signals: carbamazepine-lorazepam (Ω025 : 0.33, CRR: 2.18) and fosphenytoin-lorazepam (Ω025 : 0.99, CRR: 39.20). The TEN signals were related to the following combinations: clobazam-gabapentin (Ω025 : 0.35, CRR: 3.14), phenytoin-gabapentin (Ω025 : 0.03, CRR: 2.18), valproic acid-gabapentin (Ω025 : 0.15, CRR: 2.25), clobazam-clonazepam (Ω025 : 0.03, CRR: 2.93), clobazam-valproic acid (Ω025 : 0.29, CRR: 1.55), fosphenytoin-lamotrigine (Ω025 : 0.05, CRR: 7.37), and lacosamide-levetiracetam (Ω025 : 0.74, CRR: 1.85). This study identified two AED combinations that increased the SJS signals and seven combinations that increased the TEN signals. Although AED monotherapies require attention for SJS and TEN, some AED combinations require extra caution.

Frequency of antiepileptic drugs and response change in pediatric patients receiving 2 or more antiepileptic drugs.

Objectives:To investigate the frequency of changes in antiepileptic drugs (AEDs) use, as well as concomitant changes in the degree of seizure control in pediatric patients, who are receiving 2 or more AEDs.Methods:A prospective follow-up study at Jordan University Hospital’s pediatric neurology clinics was conducted on epileptic pediatric patients receiving at least 2 AEDs between December 2013 and April 2014. Patients were followed for 12 months.Results:A total of 82 patients were included, with a mean age of 7.2±4.7 years. The mean number of AEDs received by patients at enrollment was 2.4±0.6, and 2.5±0.7 after follow-up. Most patients (63.4%) experienced no change in seizure control, and the majority reported at least one adverse drug reaction. Most patients received lower doses than recommended, both at the beginning and end of the study. During the year, only 3 patients (4%) were eligible for dose tapering, which would then be converted to monotherapy. Follow-up appointments average was 4.2±2.9 visits/patients in one year. The frequency of medication changes and dose adjustment was very low, about one-third (29.3%) of patients requiring no change in AEDs during any follow-up visits.Conclusion:During the one year follow-up study, most patients on polytherapy maintained their level of response to the AEDs, with minimal changes in their regimen despite frequent follow-up visits. Only a small percent could be converted to AEDs monotherapy.

Clinical characteristics and fetal outcomes in women with epilepsy with planned and unplanned pregnancy: A retrospective study

PurposeTo compare the antiepileptic drug (AED) treatment patterns, seizure control, and folic acid supplementation between planned and unplanned pregnancy in women with epilepsy (WWE) and to investigate the effects of planned pregnancy on fetal outcomes. MethodsA prospectively collected database including WWE with pregnancy from Feb 2010 to Dec 2018 was retrospectively analyzed. Planned pregnancy was defined as WWE being regularly supervised by epileptologists from the time of intended pregnancy until delivery. Clinical characteristics and fetal outcomes were compared between the planned and unplanned pregnancy groups. Logistic regression was used to identify modifiable factors associated with adverse fetal outcomes. ResultsA total of 188 planned pregnancies and 289 unplanned pregnancies were enrolled in our study. Among planned pregnancies, 66.0 % took AED monotherapy, and 32.4 % received polytherapy. Among unplanned pregnancies, 58.1 % didn’t take AEDs, 28.0 % took monotherapy, and 12.8 % received polytherapy. The planned pregnancies had less generalized tonic-clonic seizures (P = 0.002) and higher proportion of being seizure-free (41.0 % vs. 22.8 %; P <0.001). All planned pregnancies took folic acid while 39.8 % of unplanned pregnancies never took it (P <0.001). The planned pregnancies had less rates of induced abortions (2.7 % vs. 13.5 %; P <0.001), preterm births (3.3 % vs. 20.4 %; P <0.001), and major congenital malformations (1.6 % vs. 7.5 %; P = 0.016). Pregnancy planning was independently associated with adverse fetal outcomes (adjusted OR, 0.14; 95 % CI, 0.08−0.27; P <0.001). ConclusionPlanned pregnancy in WWE contributes to more optimized AED pattern, better seizure control, more appropriate folic acid supplementation, and less adverse fetal outcomes.

Therapy of neonatal seizures: a two-year retrospective study at Almazov National Medical Research Centre

Introduction.Neonatal seizures are the most common pathological neurological symptom of the neonatal period, requiring immediate treatment. There are 2 directions in the treatment of seizures: relief of acute life-threatening seizures and supportive antiepileptic therapy of the chronic process. Worldwide phenobarbital is still the first-line medication for neonatal seizures. However, due to contraindications the doctors have to select and prescribe other antiepileptic therapy for both stopping seizures and supportive therapy.Objective.To introduce an algorithm for standardized phased treatment of neonatal seizures from stopping an acute debut to starting supportive chronic therapy according to clinical and electroencephalographic indications.Characteristics of children and research methods.The authors retrospectively analyzed 449 patients born in 2016 – 2017. The inclusion criteria: full-term term newborns with clinical and/or encephalographic verification of seizures in the neonatal period. The authors studied the time distribution parameters of the primary realization of seizures from the time of birth, the genesis of convulsive activity, the effectiveness of antiepileptic therapy.Results.Out of 449 treated children (full-term infants with somatic, surgical and cardiosurgical pathologies) 36 (8.0%) patients had neonatal seizures, 35 (97.33%) children of them had symptomatic seizures. Neonatal genetic epilepsy was diagnosed in 1 (2.77%) child (Otahar syndrome). The investigators revealed the prevalence of the primary realization of convulsive syndrome in newborns in the first 4 days of life. Occasionally the initial debut of seizures occurred in children older than 7 days with congenital metabolic disorders, represented by aminoaciduria. The seizures were stopped without anticonvulsants (correction of transient metabolic disorders – hypoglycemia, hypocalcemia) in 3 (8.33%) children, with phenobarbital monotherapy in 5 (13.89%) children, diazepam monotherapy in 4 (11.11%) children, monotherapy with sodium thiopental – in 5 children (13.89%), valproic acid preparations – in 8 (22.22%) children, a combination of first and second line drugs (sodium thiopental + diazepam; sodium thiopental + phenobrobital) – in 11 ( 30.56%) children. Supportive antiepileptic therapy was carried out using phenobarbital monotherapy in 16 (44.44%) children, valproic acid preparations in 7 (19.44%) children, levetiracetam in 4 (11.12%) children, oxcarbazepine in 2 (5.56 %) children; 7 (19.44%) children were discharged without supportive antiepileptic therapy.Conclusion.Currently anticonvulsant monotherapy is effective in less than 50% of neonatal seizures cases; phenobarbital or diazepam remain the first-line medications. 1/3 of the patients require a combination of antiepileptic therapy. It is of great importance to diagnose and correct transient metabolic disorders before the prescription of anticonvulsant therapy.

Treatment of epilepsy in adults: Expert opinion in South Korea

ObjectiveThe aim of this study was to gather the expert opinions of Korean epileptologists regarding the treatment of adult patients with epilepsy. MethodsA total of 42 neurologists who specialized in epilepsy were surveyed. They completed an online questionnaire describing multiple patient scenarios. Using these scenarios, they evaluated treatment strategies and gave their preference for specific antiepileptic drugs (AEDs) used to treat genetically mediated generalized epilepsy and focal epilepsy. ResultsInitial AED monotherapy, followed by a second form of alternative monotherapy or an add-on combination therapy, was the preferred treatment strategy. The experts reached consensus for 87.2% of the items. The most commonly selected AEDs for the initial monotherapy for patients with generalized epilepsy were levetiracetam or valproate. For those with focal epilepsy, levetiracetam, oxcarbazepine, or lamotrigine were the most popular selections. Ethosuximide was the treatment of choice only for patients with generalized epilepsy with prominent absence seizures. Levetiracetam was preferred as an add-on therapy for both generalized and focal epilepsy. For special populations of patients, such as elderly adults or those with comorbid diseases, levetiracetam or lamotrigine was selected as the treatment of choice. ConclusionMost of the survey results were in accordance with the US expert opinion survey published in 2016. This survey can assist clinicians in making clinical decisions when treating individual adult patients with epilepsy.

Antiepileptic drugs are not independently associated with cognitive dysfunction.

To test the hypothesis that individual antiepileptic drugs (AEDs) are not associated with cognitive impairment beyond other clinically relevant factors, we performed a cross-sectional study of patients admitted to an inpatient video-EEG monitoring unit. We prospectively enrolled patients admitted to an inpatient specialist epilepsy program between 2009 and 2016. Assessments included objective cognitive function, quality of life subscales for subjective cognitive function, and questionnaires for anxiety and depressive symptoms. Bayesian model averaging identified predictors of cognitive function. Bayesian model selection approach investigated effect of individual AEDs on cognition. Conventional frequentist analyses were also performed. A total of 331 patients met inclusion criteria. Mean age was 39.3 years and 61.9% of patients were women. A total of 45.0% of patients were prescribed AED polypharmacy, 25.1% AED monotherapy, and 29.9% no AED. Age, seizure frequency, and a diagnosis of concomitant epilepsy and psychogenic nonepileptic seizure were predictors of objective cognitive function. Depression, anxiety, and seizure frequency were predictors of subjective cognitive function. Individual AEDs were not independently associated with impaired cognitive function beyond other clinically relevant variables. This study found that no AED was independently associated with cognitive dysfunction. Significant determinants of objective and subjective cognitive dysfunction included seizure frequency and depression, respectively. These findings suggest that optimizing therapy to prevent seizures is not likely to occur at the expense of cognitive function.

Antiepileptic drug effects on subjective and objective cognition

RationaleCognitive impairment is one of the most common complaints for persons with epilepsy (PWE). These impairments are not only associated with seizures, but are also regularly reported as adverse effects of antiepileptic drugs (AEDs). Previous studies have examined cognitive effects of both AED monotherapy and polytherapy, yet there is limited research on these differences with respect to both subjective and objective cognition. The current study uses data from previous research conducted by the Centers for Disease Control and Prevention (CDC)-sponsored Managing Epilepsy Well (MEW) Network collaborative. We used three distinct archival datasets from the following: (1) the HOBSCOTCH efficacy trial at Dartmouth-Hitchcock Medical Center (HOB-1), (2) the multisite replication trial (HOB-2), and (3) epilepsy self-management research conducted at the NYU School of Medicine. MethodsThis retrospective analysis combined baseline data from three datasets to determine how the number of AEDs and the type of AEDs were associated with subjective (patient-reported) and objective (examiner-assessed) cognition. Subjective cognition was captured using the cognitive subscale of the Quality of Life in Epilepsy Inventory (QOLIE-31) in all three datasets (n = 224), while objective cognition was measured using the Repeated Battery for the Assessment of Neuropsychological Status (RBANS) in the HOB-1 dataset (n = 65) and the Brief Test of Adult Cognition by Telephone (BTACT) in the HOB-2 dataset (n = 91). Multivariable linear regression was utilized for our initial assessments, followed by propensity score matching to provide stronger control of covariates. Matching was based on significantly different covariates, such as education, depression, and history of prior epilepsy surgery. Nonparametric statistical tests were utilized to compare these matched subjects. ResultsSubjective cognitive impairment was significantly worse among individuals on polytherapy (2 + AEDs) compared with those on monotherapy (1 AED) (adjusted p = 0.041). These findings were consistent with our propensity score matched comparison of monotherapy and polytherapy, which indicated that polytherapy was associated with worse overall subjective cognition (adjusted p = 0.01), in addition to impairments on the RBANS (Total score p = 0.05) and specific subdomains of the BTACT (Episodic Verbal Memory p < 0.01, Working Memory p < 0.01, Processing Speed p < 0.01). Interestingly, older generation AEDs were associated with better language performance than newer generation and combined generation AED therapy (RBANS Language p = 0.03). These language-specific findings remained significant after controlling for the effects of topiramate and zonisamide (p = 0.04). ConclusionsA greater number of AEDs is significantly and negatively associated with subjective and objective cognition in PWE, and is in line with previous research. Antiepileptic drug type did not, in itself, appear to be associated with subjective cognition. Our findings suggest that ineffective AEDs should be replaced, rather than introducing additional AEDs to a treatment regimen. Further, while subjective and objective cognition assessments were both sensitive at detecting differences based on AED status, the neuropsychological objective subdomains offer additional and specific insights into how cognition is impaired with AEDs.

Altered plasma prostaglandin E2 levels in epilepsy and in response to antiepileptic drug monotherapy

Prostaglandin E2 (PGE2), a physiologically active lipid compound, is increased in several diseases characterized by chronic inflammation. To determine its significance in epilepsy-associated inflammation and response to antiepileptic drug (AED), we evaluated the plasma PGE2 (median, pg/ml) levels in drug-free patients with epilepsy (N = 34) and patients receiving AED monotherapy (N = 55) in addition to that in healthy controls (N = 34). When compared to controls, plasma PGE2 levels were significantly elevated in all drug-free patients independent of the type of epilepsy (137.2 versus 475.7 pg/ml, p < 0.0001). Among the patients receiving AED monotherapy, only valproate responders showed a significant decrease compared to both drug-free patients (232.1 versus 475.7 pg/ml, p < 0.01) as well as valproate non-responders (232.1 versus 611.9 pg/ml, p < 0.0001). Both responders and non-responders on phenytoin or carbamazepine monotherapy had elevated PGE2 levels similar to drug-free patients. In addition, no difference was observed in plasma profiles of PGE2 precursor, arachidonic acid among the groups. Our work presents the clinical evidence of the association between plasma PGE2 levels and valproate efficacy in patients with epilepsy.

Quality of life and its association with comorbidities and adverse events from antiepileptic medications: Online survey of patients with epilepsy in Australia

ObjectiveThis study aimed to explore the quality of life (QoL) of adult patients with epilepsy (PwE) in Australia and its relationship with comorbidities and adverse events (AEs) from antiepileptic drugs (AEDs). MethodsCross-sectional surveys were completed by PwE, or carer proxies, recruited via the online pharmacy application MedAdvisor and Australian PwE Facebook groups from May to August 2018. Data were collected on demographics, epilepsy severity and management, AEs, comorbidities, and QoL (using the Patient-Weighted Quality of Life in Epilepsy Inventory [QOLIE-10-P] total score). Two linear regression models were constructed to explore associations between AEs or comorbidities and QOLIE-10-P score, with possible confounders determined using stepwise selection. ResultsNine hundred and seventy-eight of 1267 responses were eligible (mean age of respondents: 44.5 years, 64% female, 52% employed). Recent AED use was reported by 97%; 47% were on AED monotherapy, 35% had ≤2 lifetime AEDs, and 55% were seizure-free for >1 year. After stepwise selection, control variables included in both models were time since diagnosis, employment status, seizure frequency, number of currently prescribed AEDs, and number of general practitioner (GP) visits per year. In the model for comorbidities, “psychiatric disorders” was associated with the largest QOLIE-10-P score decrease (−23.14, p < 0.001). In the model for AEs, which additionally controlled for depression and anxiety disorder, self-reported “memory problems” was associated with the largest decrease in QOLIE-10-P score (−14.27, p < 0.001). ConclusionsIn this survey of Australian PwE, many of whom had relatively well-controlled epilepsy, psychiatric and self-reported memory problems were common and associated with the greatest detrimental impact on QoL. Further research is needed to better understand the underlying causes of impaired QoL and thereby improve its management.

A study of vitamin D status in Egyptian pediatric epileptic patients on monotherapy antiepileptic drugs: a hospital-based study

Introduction and aim Epilepsy is a chronic condition with an incidence of 4–10/1000 worldwide. Antiepileptic drugs (AEDs) remain the mainstay of treatment for epilepsy. AEDs in common use are carbamazepine (CBZ), phenytoin, phenobarbitone, and sodium valproate. Long-term therapy by AEDs is associated with bone disorders, affected by both duration and dose of these drugs. The effect of antiepileptic on serum vitamin D levels is controversial and uncertain, so further clinical studies to ascertain the effect of old and newer AEDs on serum levels of vitamin D level in epileptic patients are needed, thus accomplishing a suitable usage of vitamin supplementation. The aim of this study is to assess the longitudinal effect of AEDs on serum 25-hydroxyvitamin D [25(OH) D] levels and bone mineral metabolism markers among Egyptian pediatric epileptic patients on monotherapy AEDs. Participants and methods The study was carried out on 62 epileptic patients attending the Neuropediatric Outpatient Clinic, Children's Hospital Cairo University, with history of seizures (age ranges from 1 year up to 12 years), and 64 children not on AEDs as a control group. Daily dietary intake of calories, calcium, and phosphorus was characterized by dietary recall method. Patients on valproate were 37.1% of patients, whereas 32.3% were on levetiracetam and 30.6% were on CBZ. Valproate dose ranged between 10 and 40 mg/kg/day, with a mean dose of 30.4 ± 8.1 mg/kg/day, whereas levetiracetam dose ranged between 20 and 50 mg/kg/day, with a mean dose of 26 ± 8.8 mg/kg/day, and CBZ dose ranged between 15 and 40 mg/kg/day, with a mean dose of 31.8 ± 8.9 mg/kg/day. All patients on AED and control group were evaluated for vitamin D level. Serum calcium, phosphorus, Mg, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, creatinine, and urea were measured for both patient and control groups. Results Marked vitamin D deficiency was detected in 31 epileptic patients (50%) (mean ± SD: 13.4 ± 7.6 ng/ml) compared with the control group (6.2%) (mean ± SD: 60.4 ± 17.9 ng/ml) (P = 0.000), whereas mild deficiency was remarkable in 19 patients with epilepsy (30.6%) compared with five (7.8%) controls. Overall, 54.8% of the severely deficient patients in vitamin D were on CBZ, whereas 41.9% were on valproate, and 3.2% were on levetiracetam, with statistical significance on comparing vitamin D level with the type of AEDs (P

Early detection of atherosclerotic changes associated with long use of antiepileptic drugs in epileptic patients

Objective Doppler ultrasound changes in the common carotid artery intima-media thickness (CCA IMT) and estimation of serum thiobarbituric acid reactive substances (TBARS) as predictors to the atherosclerotic complications of long use of antiepileptic drugs (AEDs). Patients and methods The study was done on 45 epileptic patients and 15 healthy individuals as a control group. All patients have been selected from the outpatient clinic of Neurology Department of Al-Zahraa University Hospital from period July 2018 to July 2020. They have been treated by monotherapy AEDs for at least 2 years. No other risk factors for atherosclerosis had been considered in these patients. They have been investigated for serum level of TBARS and Doppler ultrasound for assessment of CCA IMT. The patient group was also subdivided into three groups according to their type of treatment. Results The risk of carotid atherosclerosis in patients with epilepsy is linked with long use of older generation AEDs, namely carbamazepine and valproic acid, rather than levetiracetam which have no effect in vascular risk or CCA IMT changes. Conclusion The choice of AED therapy for long-term use should be guided with serum level of TBARS and CCA IMT as their mechanism of action as enzyme inducer might be a leading cause of vascular changes in epileptic patients.

Seizure recurrence risk in persons with epilepsy undergoing antiepileptic drug tapering.

Antiepileptic drug (AED) tapering in persons with epilepsy (PWE) after 2-3years of seizure freedom is still debatable because of the risk of seizure recurrence. Tapering patterns have wide variability and could impact seizure recurrence; this study aimed to find out the correlation between them. This prospective, observational independent assessor study enrolled PWE undergoing AED tapering in a tertiary care hospital. Data collected included demography, seizure history, AED treatment, and investigational findings. Tapering pattern was assessed based on seizure-free period and AED dose before onset of tapering, dose reduction percentage and frequency, duration of tapering, and follow-up. These variables were compared among the PWE with seizure recurrence and no seizure recurrence. Among 408 enrolled PWE, 181 were on AED monotherapy: levetiracetam (73), valproate (45), carbamazepine (44), phenytoin (16), and clobazam (3). With a minimum 19 (maximum 41months) follow-up, seizure recurrence was reported in 119 (29.2%) PWE. The seizure recurrence was not significantly different in-between mono and polytherapy groups; however, among monotherapy groups seizure recurrence was significantly higher (P=.023) in valproate (35.5%) followed by levetiracetam (28.8%) group. Parameters having significant association with seizure recurrence were duration of epilepsy (P=.03), frequency of seizures before control (P=.002), history of previously failed tapering (P=.04), and history of smoking/alcoholic/tobacco intake (P=.003). There is a wide variation in AEDs tapering pattern and seizure recurrence risk can be minimized by considering the risk factors like history of smoking/alcoholic/tobacco, longer duration of epilepsy, frequency of seizures before control, and previously failed tapering.

Effects on executive functions of antiepileptic monotherapy in pediatric age

ObjectivesCognitive abilities and executive functions in children and adolescents are important indicators of quality of life as well as academic and social achievements. Cognitive and executive functioning are often impaired in patients with epilepsy and can be exacerbated by seizures and antiseizure drugs. The aim of our observational retrospective study was to assess executive functioning in patients with pediatric epilepsy, currently taking a single antiseizure medication. Materials and methodsRecords of 172 children and adolescents aged between 6 and 18 years (mean age = 12 ± 3.4 years) with newly diagnosed epilepsy who had not yet commenced an antiepileptic treatment were included in the study. Longitudinal changes in executive functioning were assessed using the EpiTrack Junior test at baseline, before the introduction of antiepileptic monotherapy, and at 3-month, 6-month, and 9-month follow-up visits. All patients commenced a single antiepileptic treatment (levetiracetam n = 54; valproic acid n = 52; ethosuximide n = 20; oxcarbazepine n = 22; carbamazepine n = 24). Age, sex, seizure types, and seizure baseline frequency were also recorded. ResultsRelative to baseline, Epitrack Junior mean scores deteriorated at the 9-month follow-up visit for patients taking valproic acid, ethosuximide, and carbamazepine, but this was only statistically significant for patients taking carbamazepine. In contrast, mean scores improved for subjects taking levetiracetam and oxcarbazepine at the 9-month follow-up visit relative to baseline, but this was only statistically significant for patients taking levetiracetam. ConclusionsLevetiracetam was the only antiseizure medication that led to slight improvements in executive functioning; whereas carbamazepine led to deteriorations in cognitive functioning. Further research using double-blinded, placebo-controlled trials are needed to confirm these results.