Anticonvulsant Levels Research Articles

Pemantauan Kadar Obat Antiepilepsi dalam Darah terhadap Clinical Outcome pada Pasien Epilepsi di RSPAD Gatot Soebroto dengan Pendekatan Farmakokinetika

The use of antiepileptic drugs requires monitoring of blood drug levels because antiepileptics are drugs with a narrow therapeutic index. This study was conducted to determine the relationship between the accuracy of blood antiepileptic drug levels and clinical outcomes in epilepsy patients at RSPAD Gatot Soebroto using a pharmacokinetic approach. This study is an analytical observational study with a retrospective cross-sectional study of epilepsy patients using antiepileptic drugs from January 2023 to January 2024 at RSPAD Gatot Soebroto Jakarta. The results of this study showed that the most antiepileptic drug was valproic acid (38.55%). Of the 32 patients using valproic acid, there were 22 uses of valproic acid below the therapeutic range (<50 mg/L), 10 uses of valproic acid within the therapeutic range (50–100 mg/L). Of the 22 uses of phenytoin, there were 4 uses of phenytoin below the therapeutic range (<10 mg/L), 17 uses of phenytoin within the therapeutic range (10–20 mg/L), and 1 use of phenytoin above the therapeutic range (>20 mg/L). Of the 10 uses of carbamazepine, 1 use of carbamazepine was below the therapeutic range (<4 mg/L), and 9 uses of carbamazepine were within the therapeutic range (4-12 mg/L). Of the 4 uses of levetiracetam, there were 4 uses of levetiracetam below the therapeutic range (12-46 mg/L), and 1 use of oxcarbazepine had a therapeutic range below the therapeutic range (3-35 mg/L). In clinical outcomes within 6 months, 18.07% of patients experienced seizures after receiving antiepileptic drug therapy, and 81.93% of patients experienced seizure-free for up to 6 months. The conclusion of this study is that a p-value of >0.05 is obtained, which means that there is no relationship between clinical outcomes and the accuracy of antiepileptic drug levels in the blood of epilepsy patients. This is because there are other pharmacokinetic parameters that cannot be predicted, so it is necessary to monitor antiepileptic drug levels directly on patients to improve the desired clinical outcomes.

Solvent bar microextraction based on using deep eutectic solvent and multivariate optimization for simultaneous determination of antidepressant and antiepileptic drugs in biological fluids

AbstractMonitoring medications in biological fluids is an essential aspect of patient care, particularly in cases of altered mental status where accurate diagnosis, effective treatment, and even forensic examinations are crucial. In this study, a new approach combining hydrophobic-deep-eutectic and solvent-bar-microextraction (HDE-SBME) followed by a high-performance liquid chromatography-diode array detector (HPLC-DAD) was developed for the simultaneous determination of desipramine, clomipramine, as antidepressant and carbamazepine as antiepileptic agents in untreated human urine and plasma samples. The HDE solvents, synthesized using various ratios of menthol and fatty acids, were utilized in the SBME setups. Computational methods were employed to predict the structure and modes of interaction between HDE and the chosen analytes. Central composite design methodology (CCD) was used for multivariate optimization of the effects of different parameters influencing the extraction efficiency of the proposed method. Under optimized experimental conditions, the calibration graph of the spiked selected drugs in urine and plasma samples demonstrated excellent linearity (R2 ≥ 0.994), with limits of detection/quantification below 0.60/2.02 μg L−1. The extraction recoveries achieved were 88–97%, and the repeatability/reproducibility (RSD%, n = 5) was less than 6.12/7.57. The proposed method was successfully applied to determine selected drugs in patients' urine and plasma samples. The proposed method detects three drugs in patients' urine and plasma samples without using toxic volatile organic solvents. The proposed microextraction technique exhibited a confident sensitivity, feasible operation, and simplicity compared with other published methods. Thus, it can be considered a promising method for monitoring the therapeutic levels of specific antidepressant and antiepileptic drugs in urine and plasma samples.

Preparation of a β-cyclodextrin grafted magnetic biochar for efficient extraction of four antiepileptic drugs in plasma samples

Simultaneous monitoring of plasma concentration levels of multiple antiepileptic drugs (AEDs) is essential for dose adjustment in comprehensive epilepsy treatment, necessitating a sensitive technique for accurate extraction and determination of AEDs. Herein, a magnetic solid-phase extraction (MSPE) technique on the basis of modified biochar (BC) is investigated to extract four AEDs from plasma, in conjunction with high performance liquid chromatography. BC derived from Zizyphus jujuba seed shells was activated by phosphoric acid (PBC) and magnetized via coprecipitation to produce MPBC. The MPBCCD obtained after modification with β-cyclodextrin (CD) was characterized and evaluated for adsorption. It exhibited fast adsorption kinetics based on second-order kinetics and satisfactory adsorption capacity for AEDs. Then it was employed as the MSPE adsorbent and the influencing parameters were optimized. The enrichment factor was 18.75. The validation analysis revealed a favorable linearity that ranged from 0.04 to 20 μg·mL-1 along with a low limit of detection of 6.85 to 10.19 ng·mL-1. The recovery of the AEDs ranged from 78.7 to 109.2 %, with relative standard deviations below 6.7 %. Using quantum chemistry theory calculations and experimental results analysis, the adsorption mechanism was investigated. It disclosed that the suggested strategy built upon MPBCCD was appropriate for the assessment of AEDs in plasma and expanded the usage of BC as the environmentally favorable matrix for the analysis of biological samples.

Monitoring the Levels of Antiepileptic Drugs for Therapeutic Purposes: an Overview of the Current Situation and Potential Future Advancements

Antiepileptic drugs (AEDs) play a crucial role in treating epilepsy, with expected variability in their pharmacokinetics across diverse patient groups such as children, the elderly, pregnant individuals, and those undergoing polytherapy with potential drug interactions. Additionally, ensuring patient adherence is essential. Therapeutic drug monitoring (TDM) serves as a valuable tool for maintaining treatment quality. Given the prevalence of pharmacokinetic variability among AEDs, TDM enables a personalized approach to epilepsy care by allowing adjustments based on individual drug concentrations. Currently, there are 27 licensed AEDs, making them one of the most common medications subject to TDM. This review aims to provide an overview of the existing evidence on the application of AED TDM in both epilepsy and non-epilepsy conditions. The extensive pharmacokinetic variability of AEDs results in significant variations in serum concentrations among patients, making TDM beneficial for tailoring treatment to individual needs. Indications for TDM encompass scenarios where optimization of clinical outcomes is crucial. Future advancements may involve incorporating additional markers of toxicity and genetic variability to further enhance individualization and optimize AED treatment.

Joint use of population pharmacokinetics and machine learning for optimizing antiepileptic treatment in pediatric population

Purpose: Unpredictable drug efficacy and safety of combined antiepileptic therapy is a major challenge during pharmacotherapy decisions in everyday clinical practice. The aim of this study was to describe the pharmacokinetics of valproic acid (VA), lamotrigine (LTG), and levetiracetam (LEV) in a pediatric population using nonlinear mixed-effect modeling, while machine learning (ML) algorithms were applied to identify any relationships among the plasma levels of the three medications and patients’ characteristics, as well as to develop a predictive model for epileptic seizures. Methods: The study included 71 pediatric patients of both genders, aged 2–18 years, on combined antiepileptic therapy. Population pharmacokinetic (PopPK) models were developed separately for VA, LTG, and LEV. Based on the estimated pharmacokinetic parameters and the patients’ characteristics, three ML approaches were applied (principal component analysis, factor analysis of mixed data, and random forest). PopPK models and ML models were developed, allowing for greater insight into the treatment of children on antiepileptic treatment. Results: Results from the PopPK model showed that the kinetics of LEV, LTG, and VA were best described by a one compartment model with first-order absorption and elimination kinetics. Reliance on random forest model is a compelling vision that shows high prediction ability for all cases. The main factor that can affect antiepileptic activity is antiepileptic drug levels, followed by body weight, while gender is irrelevant. According to our study, children’s age is positively associated with LTG levels, negatively with LEV and without the influence of VA. Conclusion: The application of PopPK and ML models may be useful to improve epilepsy management in vulnerable pediatric population during the period of growth and development.

Ranolazine Interacts Antagonistically with Some Classical Antiepileptic Drugs-An Isobolographic Analysis.

Ranolazine, an antianginal and antiarrhythmic drug blocking slow inactivating persistent sodium currents, is described as a compound with anticonvulsant potential. Since arrhythmia often accompanies seizures, patients suffering from epilepsy are frequently co-treated with antiepileptic and antiarrhythmic drugs. The aim of this study was to evaluate the effect of ranolazine on maximal-electroshock (MES)-induced seizures in mice as well as interactions between ranolazine and classical antiepileptic drugs in this model of epilepsy. Types of pharmacodynamic interactions were established by isobolographic analysis of obtained data. The main findings of the study were that ranolazine behaves like an antiseizure drug in the MES test. Moreover, ranolazine interacted antagonistically with carbamazepine, phenytoin, and phenobarbital in the proportions of 1:3 and 1:1. These interactions occurred pharmacodynamic, since ranolazine did not change the brain levels of antiepileptic drugs measured in the fluorescence polarization immunoassay. Ranolazine and its combinations with carbamazepine, phenytoin, and phenobarbital did not impair motor coordination evaluated in the chimney test. Unfortunately, an attempt to conduct a passive avoidance task (evaluating long-term memory) resulted in ranolazine-induced delayed lethality. In conclusion, ranolazine exhibits clear-cut anticonvulsant properties in the MES test but interacts antagonistically with some antiepileptic drugs. The obtained results need confirmation in clinical studies. The mechanisms of ranolazine-induced toxicity require specific explanation.

Trimetazidine, an Anti-Ischemic Drug, Reduces the Antielectroshock Effects of Certain First-Generation Antiepileptic Drugs.

Trimetazidine (TMZ), an anti-ischemic drug for improving cellular metabolism, is mostly administered to patients with poorly controlled ischemic heart disease (IHD). Since IHD is considered the most frequent causative factor of cardiac arrhythmias, and these often coexist with seizure disorders, we decided to investigate the effect of TMZ in the electroconvulsive threshold test (ECT) and its influence on the action of four first-generation antiepileptic drugs in the maximal electroshock test (MES) in mice. The TMZ (up to 120 mg/kg) did not affect the ECT, but applied at doses of 20–120 mg/kg it decreased the antielectroshock action of phenobarbital. The TMZ (50–120 mg/kg) reduced the effect of phenytoin, and, when administered at a dose of 120 mg/kg, it diminished the action of carbamazepine. All of these revealed interactions seem to be pharmacodynamic, since the TMZ did not affect the brain levels of antiepileptic drugs. Furthermore, the combination of TMZ with valproate (but not with other antiepileptic drugs) significantly impaired motor coordination, evaluated using the chimney test. Long-term memory, assessed with a passive-avoidance task, was not affected by either the TMZ or its combinations with antiepileptic drugs. The obtained results suggest that TMZ may not be beneficial as an add-on therapy in patients with IHD and epilepsy.

Pre-pregnancy and antenatal care of women with epilepsy

BackgroundEpileptic seizures in pregnancy pose a significant risk to both the mother and fetus. There is little evidence of the impact of pre-pregnancy counselling (PPC) and specialist multi-disciplinary antenatal care on a pregnancy.ObjectivesTo determine critical components of care in preventing seizures and adverse outcomes in pregnancies of women with epilepsy.MethodA retrospective cohort study of pregnant women with epilepsy. Participants were seen in the Neuro-Obstetrics multidisciplinary clinic based in West London from 2012 to 2020.ResultsA total of 150 patients; including 242 pregnancies, were analysed. Of these pregnancies, 69 were reported to have had at least 1 seizure. The anti-epileptic drug profiles and dosages were recorded in each group; 71.5% of pregnancies involved anti-epileptic drugs (AEDs), 68.8% of these patients were on mono-therapy and 22.5% were on dual-therapy. Patients without access to PPC or specialist antenatal care had less frequent monitoring of AED levels, fewer dosage adjustments and a higher seizure frequency during the pregnancy. In 9.1% of pregnancies a new AED was started.ConclusionThese data support the use of PPC in preventing seizures in early pregnancy. The data also shows a reduction in seizure frequency following specialist multidisciplinary antenatal care.mtm116@ic.ac.uk

0628 Epilepsy Control and Night Sleep Duration and Afternoon Siesta

Abstract Introduction The relationship between sleep and epilepsy has long been recognized but understanding the association between seizure control and sleep duration is not well explored. The study aims to describe the sleep habits in people with epilepsy (PwE) and explore the association between sleep habits, particularly afternoon napping and level of seizure control and anti-epileptic drugs (AEDs). Methods this is a cross-sectional study of adult epilepsy patients attending neurology clinic. Sleep parameters are measured using actigraphy for one week and home sleep apnea testing to rule out obstructive sleep apnea (OSA). Results total of 250 PwE were screened and 129 patients (male & female) completed the study with mean age of 29.75 ± 9.18 years and mean body mass index (BMI) of 27.12 kg/m2. There was significant association between night sleep duration and time of wake up and number of AEDs (adjusted R2=0.026, P=0.03 & P=0.04 respectively). There is also significant association between number of seizures per night and afternoon napping (adjusted R2=0.043, P=0.05). Other sleep parameters did not reveal any significant association with level of epilepsy control neither with number of AEDs (P>0.05). Conclusion The study described that PwE with uncontrolled epilepsy on multiple AEDs are practicing sleep habits that involved longer afternoon napping and shorter sleep duration. Support (If Any) Sultan Qaboos University

Current Aspects of Antiepileptic Therapy in Pregnant Women

Achieving a high quality of life in patients with epilepsy is of paramount importance not only for neurologists, but also for allied professionals who guide patients through the subsequent stages of treatment after diagnosis. This is of particular relevance to patients in the gestational period. Literature suggests that 13% of women experience an exacerbation of epilepsy during pregnancy, which is due to a reduction in plasma levels of antiepileptic drugs (PEPs) due to increased metabolism. However, 14% of women have seizures exclusively during pregnancy.

Pharmacokinetic changes for newer antiepileptic drugs and seizure control during pregnancy.

ObjectiveTo investigate pharmacokinetic changes in newer antiepileptic drugs (AEDs) and assess seizure frequencies and risk factors of increased seizures during pregnancy in women with epilepsy (WWE).MethodsA total of 56 pregnancies in 53 WWE who received newer antiepileptic drugs (AEDs) were enrolled. Data on seizure activity and types, daily dose, and AEDs blood levels were derived from routine clinical follow‐up. Changes in AEDs clearance were compared between each trimester and nonpregnant baseline. The ratio of AED levels of each trimester to their targets (nonpregnant baseline) concentrations (RTC) was compared between patients with and without an increased seizure. A binary logistic regression was used to investigate the risk factors contributing to seizure worsening during pregnancy.ResultsIncreased clearances of LTG, LEV, and OXC were observed in all trimesters versus nonpregnant baseline. The peak changes in the clearance of LTG (3.42‐fold baseline clearance) (p < 0.001) and LEV (2.78‐fold) (p < 0.001) occurred in the second trimester during pregnancy, followed by oxcarbazepine (2.11‐fold) in the third trimester (p < 0.03). Plasma concentrations of LTG and LEV during pregnancy were significantly decreased compared to baseline levels, except for OXC. However, no significant differences in RTC values were observed between patients with and without seizure worsening. Some risk factors as seizures for the prior nine months could significantly affect seizure frequency during pregnancy.ConclusionWe found substantial changes in the pharmacokinetics of multiple newer AEDs in WWE, reinforcing the need for therapeutic drug monitoring (TDM) during pregnancy. We would encourage at least one monitoring every trimester and probably more frequently for women with poorly seizure control before pregnancy, and AEDs dose adjustment should keep up with clearance changes. In addition, a well‐controlled seizure nine months before pregnancy could lower the risks of seizure during pregnancy, highlighting the importance of pre‐pregnancy counseling and seizure management before pregnancy.

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.

Pemantauan Kadar Obat Antiepilepsi secara Farmakokinetika Terhadap Clinical Outcome pada Pasien Pediatrik

The high prevalence of antiepileptic drug use in pediatrics increases the risk of side and toxic effects; therefore, it is necessary to monitor drug levels. Therapeutic drug monitoring is conducted through pharmacokinetics by calculating blood drug levels based on respondents' dose and frequency of therapy. This study aimed to determine the pharmacokinetics of antiepileptic drug levels and the correlation with clinical outcomes using descriptive observational design. Furthermore, the Indonesian Epilepsy Community collected respondents' data from June to July 2020 through online and telephone interviews. Out of the 11 respondents that recieved phenytoin, only 1 (9.09%) was in the therapeutic range (10–20 mg/L), while 10 (90.91%) were outside the therapeutic range (&lt;10mg/L). From the 14 respondents that received phenobarbital, 8 (57.14%) were in the therapeutic range (15–40 mg/L), and 6 (42.86%) were outside the therapeutic range (&lt;15 mg/L and &gt;40 mg/L). From the 47 respondents that received valproic acid, 23 were administered through monotherapy, 7 (30.44%) were in the therapeutic range (50–100 mg/L), and 16 (69.56%) were outside the therapeutic range (&lt;50 mg/L and &gt;100mg/L). Out of the 24 respondents that received valproic acid as monotherapy, 18 (75%) were in the therapeutic range (50–100 mg/L), and 6 (25%) were outside the therapeutic range (&lt;50 mg/L and &gt;100mg/L). The results showed that there was no significant relationship (p&gt;0.05) between drug levels and clinical outcome in respondents treated with either monotherapy or polytherapy of valproic acid. In conclusion, a total of 38 respondents (52.05%) had drugs levels outside the therapeutic range, while 35 (47.95%) had drug levels in the therapeutic range. Furthermore, respondents with drug levels outside the therapeutic range require direct monitoring of antiepileptic drug levels to avoid toxic effects and improve clinical outcomes.

Ion-Channel Antiepileptic Drugs: An Analytical Perspective on the Therapeutic Drug Monitoring (TDM) of Ezogabine, Lacosamide, and Zonisamide

The term seizures includes a wide array of different disorders with variable etiology, which currently represent one of the most important classes of neurological illnesses. As a consequence, many different antiepileptic drugs (AEDs) are currently available, exploiting different activity mechanisms and providing different levels of performance in terms of selectivity, safety, and efficacy. AEDs are currently among the psychoactive drugs most frequently involved in therapeutic drug monitoring (TDM) practices. Thus, the plasma levels of AEDs and their metabolites are monitored and correlated to administered doses, therapeutic efficacy, side effects, and toxic effects. As for any analytical endeavour, the quality of plasma concentration data is only as good as the analytical method allows. In this review, the main techniques and methods are described, suitable for the TDM of three AEDs belonging to the class of ion channel agents: ezogabine (or retigabine), lacosamide, and zonisamide. In addition to this analytical overview, data are provided, pertaining to two of the most important use cases for the TDM of antiepileptics: drug–drug interactions and neuroprotection activity studies. This review contains 146 references.

DISCONTINUATION (СANCELLATION) OF TREATMENT OF EPILEPTIC SEIZURES

Currently, special attention is paid to the quality of life of patients with epilepsy. Therefore, great importance is given to the possibility of canceling antiepileptic therapy with prolonged remission. Before discontinuation of therapy, it is necessary to conduct electroencephalography (EEG) and determine the level of antiepileptic drugs (AED) in blood plasma. The presence of signs of typical epileptic activity on the EEG is a likely question of the correctness of the chosen tactics and the need to identify possible symptomatic mild seizures has no clearly defined standards for reducing the dosage of AED. On the recommendation of some experts, benzodiazepines and barbiturates are canceled within 4-8 weeks, with a combination therapy with a break for each drug of 1 month for 4-8 weeks for each.

P12.01 The effectiveness of antiepileptic drug treatment in glioma patients: lamotrigine versus lacosamide

Abstract BACKGROUND Optimal treatment with antiepileptic drugs (AEDs) is an important part of care for brain tumor patients with epileptic seizures. Lamotrigine and lacosamide are both examples of frequently used non-enzyme inducing AEDs with limited to no drug-drug interactions, reducing the risk of unfavorable side effects. This study aimed to compare the effectiveness of lamotrigine versus lacosamide. MATERIAL AND METHODS In this multicenter study we retrospectively analyzed data of patients with diffuse grade 2–4 glioma with epileptic seizures. All patients received either lamotrigine or lacosamide during the course of their disease after treatment failure of first-line monotherapy with levetiracetam or valproic acid. Primary outcome was the cumulative incidence of treatment failure, from initiation of lamotrigine or lacosamide, with death as competing event, for which a competing risk model was used. Secondary outcomes were uncontrolled seizures after AED initiation and level of toxicity. RESULTS We included a total of 139 patients of whom 61 (44%) used lamotrigine and 78 (56%) used lacosamide. At 12 months, there was no statistically significant difference in the cumulative incidence of treatment failure for any reason between lamotrigine and lacosamide: 38% (95%CI: 26–51%) versus 30% (95%CI: 20–41%), respectively. The adjusted hazard ratio for treatment failure of lacosamide compared to lamotrigine was 0.84 (95%CI: 0.46–1.56). The cumulative incidences of treatment failure due to uncontrolled seizures (18% versus 11%) and due to adverse events (17% versus 19%) did not differ significantly between lamotrigine and lacosamide. CONCLUSION Lamotrigine and lacosamide show similar effectiveness in diffuse glioma patients with epilepsy.

The effectiveness of antiepileptic drug treatment in glioma patients: lamotrigine versus lacosamide

PurposeOptimal treatment with antiepileptic drugs (AEDs) is an important part of care for brain tumor patients with epileptic seizures. Lamotrigine and lacosamide are both examples of frequently used non-enzyme inducing AEDs with limited to no drug-drug interactions, reducing the risk of unfavorable side effects. This study aimed to compare the effectiveness of lamotrigine versus lacosamide.MethodsIn this multicenter study we retrospectively analyzed data of patients with diffuse grade 2–4 glioma with epileptic seizures. All patients received either lamotrigine or lacosamide during the course of their disease after treatment failure of first-line monotherapy with levetiracetam or valproic acid. Primary outcome was the cumulative incidence of treatment failure, from initiation of lamotrigine or lacosamide, with death as competing event, for which a competing risk model was used. Secondary outcomes were uncontrolled seizures after AED initiation and level of toxicity.ResultsWe included a total of 139 patients of whom 61 (44%) used lamotrigine and 78 (56%) used lacosamide. At 12 months, there was no statistically significant difference in the cumulative incidence of treatment failure for any reason between lamotrigine and lacosamide: 38% (95%CI 26–51%) versus 30% (95%CI 20–41%), respectively. The adjusted hazard ratio for treatment failure of lacosamide compared to lamotrigine was 0.84 (95%CI 0.46–1.56). The cumulative incidences of treatment failure due to uncontrolled seizures (18% versus 11%) and due to adverse events (17% versus 19%) did not differ significantly between lamotrigine and lacosamide.ConclusionLamotrigine and lacosamide show similar effectiveness in diffuse glioma patients with epilepsy.

SNO and EANO practice guideline update: Anticonvulsant prophylaxis in patients with newly diagnosed brain tumors.

To update the 2000 American Academy of Neurology (AAN) practice parameter on anticonvulsant prophylaxis in patients with newly diagnosed brain tumors. Following the 2017 AAN methodologies, a systematic literature review utilizing PubMed, EMBASE Library, Cochrane, and Web of Science databases was performed. The studies were rated based on the AAN therapeutic or causation classification of evidence (class I-IV). Thirty-seven articles were selected for final analysis. There were limited high-level, class I studies and mostly class II and III studies. The AAN affirmed the value of these guidelines. In patients with newly diagnosed brain tumors who have not had a seizure, clinicians should not prescribe antiepileptic drugs (AEDs) to reduce the risk of seizures (level A). In brain tumor patients undergoing surgery, there is insufficient evidence to recommend prescribing AEDs to reduce the risk of seizures in the peri- or postoperative period (level C). There is insufficient evidence to support prescribing valproic acid or levetiracetam with the intent to prolong progression-free or overall survival (level C). Physicians may consider the use of levetiracetam over older AEDs to reduce side effects (level C). There is insufficient evidence to support using tumor location, histology, grade, molecular/imaging features when deciding whether or not to prescribe prophylactic AEDs (level U).

Sudden unexpected death in epilepsy: Experience of neurologists in Saudi Arabia

Sudden unexpected death in epilepsy (SUDEP) may account for up to 17% of all deaths in epilepsy. However, it is unknown if neurologists discuss this risk with patients. This study aimed to examine the understanding and practices of SUDEP by neurologists in Saudi Arabia. An electronic web-based survey was sent to 125 neurologists using the mailing list of the Saudi Neurology Society. The survey questions included respondents' demographics, frequency of SUDEP discussion, reasons for discussing/not discussing SUDEP, and perceived patient reactions. Respondents' knowledge of the SUDEP risk factors was examined using 12 items from the currently available literature. Logistic regression analyses were applied to examine the factors that influence the frequency of SUDEP discussions and perceived patient reactions. The participants were neurologists who had completed postgraduate training, devoted >5% of their time to clinical care, and had at least one patient with epilepsy in their independent neurology clinic. A total of 60 respondents met the eligibility criteria and completed the surveys. Of them, 25% discussed SUDEP most of the time, 65% sometimes or rarely, and 10% never discussed it. Of those who discussed SUDEP with their patients, 63.3% did it if the patient was at high risk. Poor compliance with antiepileptic drugs (AEDs) was the most common patient factor highlighted (81.7%). The perceived patients' reactions were variable, with positive reactions (motivation to comply and appreciation) being the most frequent. The majority of respondents (78.3%) had incomplete understanding of the published SUDEP risk factors, with SUDEP knowledge scores ≤2.5 (≤50% of the possible total score). The most identified risk factors were frequent generalized tonic-clonic seizures (83.3%), long duration of epilepsy (53.3%), lack of use or sub-therapeutic levels of AEDs (50%), and AED polytherapy (50%). No association was found between how often SUDEP was discussed and other factors, including training in epilepsy, ≥10 years in practice, seeing ≥100 patients, and having SUDEP cases in the past two years. It was found that patients positively reacted to discussion on SUDEP if neurologists had a good understanding of the SUDEP risk factors (χ2 = 5.773, p = 0.016). Neurologists in Saudi Arabia do not often discuss SUDEP with patients that have epilepsy. Moreover, when they do, they stress a more individualized approach despite having only a limited understanding of the SUDEP risk factors. Our findings suggest that more guidance should be provided to practitioners on how best to counsel their patients about SUDEP.

English

A seizure is a brief disturbance of cerebral function, lasting from seconds to a few minutes, caused by an abnormal electrical discharge. Epilepsy is the tendency to have seizures on a chronic, recurrent basis, not resulting from a temporary condition. The term, epilepsy, does not presuppose a cause; there are many causes. Essentially, anything that disturbs the normal functioning of the cerebral cortex can cause seizures, and if this abnormality is enduring, it can result in epilepsy.1 Epilepsy is a common neurological condition with a global prevalence of 1.2 %. Most women with epilepsy who become pregnant or are planning to conceive are recommended to continue taking antiepileptic drugs (AEDs) to minimise seizure recurrence during pregnancy, adverse effects to the fetus, and unintended ill consequences during labour and / or delivery.2,3 The seizure pattern during pregnancy may be influenced by variations in ovarian hormones, blood levels of antiepileptic drugs, and metabolic changes.4 Status epilepticus occurs in only 1 – 2 % of pregnancies,5 and if treated appropriately and aggressively carries a fairly low risk of morbidity and mortality. Structural and metabolic changes may precipitate new-onset seizures during pregnancy. The structural causes include intracranial haemorrhage of multiple types, cerebral venous sinus thrombosis, and ischemic stroke. Metabolic causes include hyperemesis gravidarum; acute hepatitis (due to fatty liver of pregnancy or viral hepatitis); metabolic diseases, such as acute intermittent porphyria; infections, such as malaria; and eclampsia.5 Evaluation and management should be performed in a stepwise fashion and may require a multidisciplinary approach with other specialties such as neurology.6 The threat of seizures during pregnancy and the consequences that they might have on the developing foetus are fundamental reasons for the prescription of daily antiepileptic medication to a pregnant woman with epilepsy (WWE).7 We present an original case of 3 episodes of seizures, of 22-year-old female who was 16 weeks pregnant. This study was approved by Sree Uthradom Thirunal Hospital, Pattom, Trivandrum, Kerala (ethics committee).