Comparative analysis of dexmedetomidine, midazolam, and propofol impact on epilepsy-related mortality in the ICU: insights from the MIMIC-IV database.

BACKGROUND: Dexmedetomidine (Dex), midazolam, and propofol are three distinct sedatives characterized by varying pharmacological properties. Previous literature has indicated the positive impact of each of these sedatives on ICU patients. However, there is a scarcity of clinical evidence comparing the efficacy of Dex, midazolam, and propofol in reducing mortality among people with epilepsy (PWE). This study aimed to assess the impact of Dex, midazolam, and propofol on the survival of PWE. METHODS: The data were retrospectively retrieved from the Medical Information Mart for Intensive Care (MIMIC)-IV database (version 2.0). PWE were categorized into Dex, midazolam, and propofol groups based on the intravenously administered sedatives. PWE without standard drug therapy were included in the control group. Comparative analyses were performed on the data among the groups. RESULTS: The Dex group exhibited a significantly lower proportion of in-hospital deaths and a markedly higher in-hospital survival time compared to the midazolam and propofol groups (p < 0.01) after propensity score matching. Kaplan-Meier curves demonstrated a significant improvement in survival rates for the Dex group compared to the control group (p = 0.025). Analysis of Variance (ANOVA) revealed no significant differences in survival rates among the Dex, midazolam, and propofol groups (F = 1.949, p = 0.143). The nomogram indicated that compared to midazolam and propofol groups, Dex was more effective in improving the survival rate of PWE. CONCLUSION: Dex might improve the survival rate of PWE in the ICU compared to no standard drug intervention. However, Dex did not exhibit superiority in improving survival rates compared to midazolam and propofol.

Multi-target Phenylpropanoids Against Epilepsy.

Epilepsy is a neurological disease with no defined cause, characterized by recurrent epileptic seizures. These occur due to the dysregulation of excitatory and inhibitory neurotransmitters in the central nervous system (CNS). Psychopharmaceuticals have undesirable side effects; many patients require more than one pharmacotherapy to control crises. With this in mind, this work emphasizes the discovery of new substances from natural products that can combat epileptic seizures. Using in silico techniques, this review aims to evaluate the antiepileptic and multi-target activity of phenylpropanoid derivatives. Initially, ligand-based virtual screening models (LBVS) were performed with 468 phenylpropanoid compounds to predict biological activities. The LBVS were developed for the targets alpha- amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), voltage-gated calcium channel Ttype (CaV), gamma-aminobutyric acid A (GABAA), gamma-aminobutyric acid transporter type 1 (GAT-1), voltage-gated potassium channel of the Q family (KCNQ), voltage-gated sodium channel (NaV), and N-methyl D-aspartate (NMDA). The compounds that had good results in the LBVS were analyzed for the absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters, and later, the best molecules were evaluated in the molecular docking consensus. The TR430 compound showed the best results in pharmacokinetic parameters; its oral absorption was 99.03%, it did not violate any Lipinski rule, it showed good bioavailability, and no cytotoxicity was observed either from the molecule or from the metabolites in the evaluated parameters. TR430 was able to bind with GABAA (activation) and AMPA (inhibition) targets and demonstrated good binding energy and significant interactions with both targets. The studied compound showed to be a promising molecule with a possible multi-target activity in both fundamental pharmacological targets for the treatment of epilepsy.

Epilepsy, Antiepileptic Drugs, and Adverse Pregnancy Outcomes, 1: Examination and Interpretation of Recent Research.

The age-standardized global prevalence of epilepsy is about 0.3% in women. Seizures are associated with morbidity and mortality risks; so, women with epilepsy (WWE) are usually advised antiepileptic drug (AED) treatment even during pregnancy. Women may also knowingly or unknowingly be exposed during pregnancy to AEDs advised for other on- or off-label indications. In this context, a meta-analysis of 35 adverse gestational outcomes examined in 76 observational studies found that WWE were at increased risk of most of the adverse outcomes, regardless of gestational exposure to AEDs. AEDs, especially in polytherapy, further increased at least a few of the gestational risks, including risks of congenital conditions, neonatal intensive care unit admission, small for gestational age, low birth weight, and neonatal/infant death (it is unclear whether the lack of statistical significance for the remaining risks was because AED exposure was truly limited to these risks or whether the nonsignificant analyses were underpowered). Reassuringly, the increases in risk were mostly in the small to modest range. This meta-analysis pooled unadjusted risks (which would probably be larger than adjusted risks), so readers are informed about expected findings in the population but not about cause-effect relationships that may be cautiously hypothesized from adjusted analyses. A take-home message is that, because of the wide range of outcomes for which risk is increased, WWE should be closely monitored and followed all through pregnancy, regardless of treatment with AEDs. This article also provides readers with suggestions on how to critically interpret literature with regard to 8 matters: confounding by indication and confounding by severity of indication, as specific to the indication for AED prescription; unadjusted and adjusted analyses; the base rate of an outcome in the population; the examination of multiple outcomes; the uniform direction of findings; the sample numbers; the timing of AED exposure; and self-fulfilling prophecies.

Effect of SCN1Aand SCN2A gene polymorphisms on the efficacy of valproic acid treatment in Chinese children with epilepsy.

OBJECTIVE: Epilepsy patients exhibit considerable differences in their response to sodium valproate (VPA) therapy, a phenomenon that might be attributed to individual genetic variances. The role of genetic variations, specifically in sodium channels encoded by SCN1A and SCN2A genes, in influencing the effectiveness of VPA in treating epilepsy is still debated. This research focuses on examining the impact of these genetic polymorphisms on the efficacy of VPA therapy among pediatric epilepsy patients in China. METHODS: Five single nucleotide polymorphisms (SNPs), including SCN1A (rs10188577, rs2298771, rs3812718) and SCN2A (rs2304016, rs17183814), were genotyped in 233 epilepsy patients undergoing VPA therapy. The associations between genotypes and the antiepileptic effects of VPA were assessed, with 128 patients categorized as VPA responders and 105 as VPA non-responders. RESULTS: In the context of VPA monotherapy, SCN1A rs2298771 and SCN2A rs17183814 were found to be significantly associated with VPA response (P< 0.05). CONCLUSION: Our study suggests the findings of this investigation indicate that the polymorphisms SCN1A rs2298771 and SCN2A rs17183814 could potentially act as predictive biomarkers for the responsiveness to VPA among Chinese epilepsy patients.

New data-driven method to predict the therapeutic indication of redeemed prescriptions in secondary data sources: a case study on antiseizure medications users aged ≥65 identified in Danish registries.

OBJECTIVES: We aimed to develop a new data-driven method to predict the therapeutic indication of redeemed prescriptions in secondary data sources using antiepileptic drugs among individuals aged ≥65 identified in Danish registries. DESIGN: This was an incident new-user register-based cohort study using Danish registers. SETTING: The study setting was Denmark and the study period was 2005-2017. PARTICIPANTS: Participants included antiepileptic drug users in Denmark aged ≥65 with a confirmed diagnosis of epilepsy. PRIMARY AND SECONDARY OUTCOME MEASURES: Sensitivity served as the performance measure of the algorithm. RESULTS: The study population comprised 8609 incident new users of antiepileptic drugs. The sensitivity of the algorithm in correctly predicting the therapeutic indication of antiepileptic drugs in the study population was 65.3% (95% CI 64.4 to 66.2). CONCLUSIONS: The algorithm demonstrated promising properties in terms of overall sensitivity for predicting the therapeutic indication of redeemed antiepileptic drugs by older individuals with epilepsy, correctly identifying the therapeutic indication for 6 out of 10 individuals using antiepileptic drugs for epilepsy.

Spectrum of NMDA Receptor Variants in Neurodevelopmental Disorders and Epilepsy.

N-methyl-D-aspartate receptors (NMDAR) are ligand-gated ion channels mediating excitatory neurotransmission and are important for normal brain development, cognitive abilities, and motor functions. Pathogenic variants in the Glutamate receptor Ionotropic N-methyl-D-aspartate (GRIN) genes (GRIN1, GRIN2A-D) encoding NMDAR subunits have been associated with a wide spectrum of neurodevelopmental disorders and epilepsies ranging from treatable focal epilepsies to devastating early-onset developmental and epileptic encephalopathies. Genetic variants in NMDA receptor genes can cause a range of complex alterations to receptor properties resulting in various degrees of loss-of-function, gain-of-function, or mixtures thereof. Understanding how genetic variants affect the function of the receptors, therefore, represents an important first step in the ongoing development towards targeted therapies. Currently, targeted treatment options for GRIN-related diseases are limited. However, treatment with memantine has been reported to significantly reduce seizure frequency in a few individuals with developmental and epileptic encephalopathies harboring de novo gain-of-function GRIN2A missense variants, and supplementary treatment with L-serine has been associated with improved motor and cognitive performance as well as reduced seizure frequency in patients with GRIN2B loss-of-function missense variants as well as GRIN2A and GRIN2B null variants.

Teratogenesis, Perinatal, and Neurodevelopmental Outcomes After In Utero Exposure to Antiseizure Medication: Practice Guideline From the AAN, AES, and SMFM.

This practice guideline provides updated evidence-based conclusions and recommendations regarding the effects of antiseizure medications (ASMs) and folic acid supplementation on the prevalence of major congenital malformations (MCMs), adverse perinatal outcomes, and neurodevelopmental outcomes in children born to people with epilepsy of childbearing potential (PWECP). A multidisciplinary panel conducted a systematic review and developed practice recommendations following the process outlined in the 2017 edition of the American Academy of Neurology Clinical Practice Guideline Process Manual. The systematic review includes studies through August 2022. Recommendations are supported by structured rationales that integrate evidence from the systematic review, related evidence, principles of care, and inferences from evidence. The following are some of the major recommendations. When treating PWECP, clinicians should recommend ASMs and doses that optimize both seizure control and fetal outcomes should pregnancy occur, at the earliest possible opportunity preconceptionally. Clinicians must minimize the occurrence of convulsive seizures in PWECP during pregnancy to minimize potential risks to the birth parent and to the fetus. Once a PWECP is already pregnant, clinicians should exercise caution in attempting to remove or replace an ASM that is effective in controlling generalized tonic-clonic or focal-to-bilateral tonic-clonic seizures. Clinicians must consider using lamotrigine, levetiracetam, or oxcarbazepine in PWECP when appropriate based on the patient's epilepsy syndrome, likelihood of achieving seizure control, and comorbidities, to minimize the risk of MCMs. Clinicians must avoid the use of valproic acid in PWECP to minimize the risk of MCMs or neural tube defects (NTDs), if clinically feasible. Clinicians should avoid the use of valproic acid or topiramate in PWECP to minimize the risk of offspring being born small for gestational age, if clinically feasible. To reduce the risk of poor neurodevelopmental outcomes, including autism spectrum disorder and lower IQ, in children born to PWECP, clinicians must avoid the use of valproic acid in PWECP, if clinically feasible. Clinicians should prescribe at least 0.4 mg of folic acid supplementation daily preconceptionally and during pregnancy to any PWECP treated with an ASM to decrease the risk of NTDs and possibly improve neurodevelopmental outcomes in the offspring.

Innovative LC-MS/MS method for therapeutic drug monitoring of fenfluramine and cannabidiol in the plasma of pediatric patients with epilepsy.

We present a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying fenfluramine (FFA), its active metabolite norfenfluramine (norFFA), and Epidyolex®, a pure cannabidiol (CBD) oral solution in plasma. Recently approved by the EMA for the adjunctive treatment of refractory seizures in patients with Dravet and Lennox-Gastaut syndromes aged above 2 years, FFA and CBD still do not have established therapeutic blood ranges, and thus need careful drug monitoring to manage potential pharmacokinetic and pharmacodynamic interactions. Our method, validated by ICH guidelines M10, utilizes a rapid extraction protocol from 100 µL of human plasma and a reversed-phase C-18 HPLC column, with deuterated internal standards. The Thermofisher Quantiva triple-quadrupole MS coupled with an Ultimate 3000 UHPLC allowed multiple reaction monitoring detection, ensuring precise analyte quantification. The assay exhibited linear responses across a broad spectrum of concentrations: ranging from 1.64 to 1000 ng/mL for both FFA and CBD, and from 0.82 to 500 ng/mL for norFFA. The method proves accurate and reproducible, free from matrix effect. Additionally, FFA stability in plasma at 4 °C and -20 °C for up to 7 days bolsters its clinical applicability. Plasma concentrations detected in patients samples, expressed as mean ± standard deviation, were 0.36 ± 0.09 ng/mL for FFA, 19.67 ± 1.22 ng/mL for norFFA. This method stands as a robust tool for therapeutic drug monitoring (TDM) of FFA and CBD, offering significant utility in assessing drug-drug interactions in co-treated patients, thus contributing to optimized patient care in complex therapeutic scenarios.

Efficacy and safety of herbal medicine combined with acupuncture in pediatric epilepsy treatment: A meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the efficacy and safety of herbal medicine and acupuncture combination for pediatric epilepsy treatment. METHODS: Databases were searched from their interception until October 2023 to identify randomized controlled trials focusing on the therapeutic efficacy of herbal medicine-acupuncture combination (intervention group) for pediatric epilepsy. The primary outcome was the risk of treatment failure, whereas the secondary outcomes included the risk of post-treatment electroencephalogram (EEG) abnormalities and adverse events. Subgroup analyses were conducted based on the type of herbal compound formulas. Meta-regression analysis was conducted to examine the influence of patient demographics and clinical history on the therapeutic efficacy of herbal medicine-acupuncture combination for pediatric epilepsy. To assess the cumulative evidence, trial sequential analysis (TSA) was performed. RESULTS: The analysis included 10 trials involving a total of 882 pediatric patients. Meta-analysis revealed that the intervention group had a lower risk of treatment failure than the control group (risk ratio [RR] = 0.3, 95% confidence interval [CI]: 0.19-0.47, P<0.00001, I2 = 0%, 10 trials). Subgroup analyses showed that therapeutic efficacy was consistent among the different herbal compound formulas. Meta-regression analysis revealed that the efficacy of the treatments did not significantly vary with patient age, male sex, and duration of seizure history. TSA suggested that herbal medicine-acupuncture combination exerted a robust and conclusive effect on seizure treatment. Although the combined used of herbal medicine and acupuncture was not associated with a lower risk of post-treatment EEG abnormalities (RR = 0.82, 95%CI:0.6-1.11, P = 0.2, 3 trials), the risk of adverse events was reduced (RR = 0.27, 95%CI:0.18-0.41, P<0.00001, 4 trials). CONCLUSION: The meta-analysis suggested that combined use of herbal medicine and acupuncture is a promising and safe clinical approach for pediatric epilepsy treatment. Further large-scale studies are necessary to conclusively determine the efficacy and safety of herbal medicine and acupuncture in pediatric epilepsy treatment.

Therapeutic Drug Monitoring of Levetiracetam in Different Trimesters of Pregnant Women with Epilepsy in a Tertiary Care Center: A Prospective Study.

BACKGROUND: Levetiracetam is the most commonly used antiepileptic drug in pregnant women due to its low teratogenic risk profile, favorable pharmacokinetic characteristics, and safety profile. Serum levels of levetiracetam vary in epilepsy during pregnancy. Therefore, the aim of the study was to evaluate the serum levels of levetiracetam during different trimesters of pregnancy by using therapeutic drug monitoring (TDM). MATERIALS AND METHODS: This was a single-center, prospective study. Pregnant women with epilepsy on levetiracetam were enrolled after getting written informed consent from them. Serum trough levels of levetiracetam were estimated at all trimesters by high-performance liquid chromatography (HPLC). RESULTS: The study included 16 participants with mean ± standard deviation (SD) age of 27.75 ± 4 years. There were nine (56.2%) participants with generalized seizure disorder and seven (43.8%) participants of focal seizure disorder. Among 16 patients, 10 (62.5%) participants were on levetiracetam alone and six (37.5%) participants were on levetiracetam combined with other antiepileptic drugs. In a total of 48 trough samples, 45 sample concentrations were below the therapeutic range of 12-46 mg/l and three sample concentrations were within the therapeutic range. There was a statistically significant difference in the concentration-dose ratio (CDR) of levetiracetam between the third and first trimesters (P-value 0.018). CONCLUSION: There was a statistically significant difference in serum levetiracetam concentration between the third and first trimesters. A well-conducted, intensive pharmacokinetic sampling study in PWWE with a control group is needed in future to evaluate the whole pharmacokinetic profile of levetiracetam and to correlate the clinical outcome.

Association of Prenatal Exposure to Antiseizure Medications With Creative and Executive Function at Age 4.5 Years.

BACKGROUND AND OBJECTIVES: Neurodevelopmental effects of fetal antiseizure medication (ASM) exposure on creativity and executive functions are poorly understood. We previously found fetal valproate exposure to adversely affect measures of creativity and executive functions. In this study, we examine fetal exposure of newer ASMs on these functions in children of women with epilepsy (WWE) compared with children of healthy women (HW). METHODS: The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs study is a multicenter NIH-funded prospective observational cohort study of WWE and HW enrolled in pregnancy and their offsprings. This report examines blindly assessed creativity and executive functions in 4.5-year-old children of WWE vs HW. In addition, exposure-dependent ASM effects during the third trimester were examined in children of WWE, using a ratio of maximum observed ASM concentrations and ratio of defined daily dose (ratio DDD). For polytherapy, ratios were summed across ASMs. Linear regression models adjusted for multiple potential confounding factors were conducted for all analyses. The primary outcome for 4.5-year-old children was the Torrance Test of Creative Thinking-Figural Creativity Index. Secondary outcomes included the Global Executive Composite Score from the Behavior Rating Inventory of Executive Function-Preschool Version and subscales and other indexes of both measures. RESULTS: The primary analysis included 251 children of WWE and 73 of HW. No differences in creativity or executive function were found between children of WWE vs HW. No ASM exposure-dependent effects were found for the creativity measures, but exposure-dependent effects for executive function were present for ratio ASM concentration and ratio DDD. DISCUSSION: Our findings at 4.5 years show no differences in creative thinking between children of WWE vs HW (-3.2 [-9.0 to 2.7], p = 0.286) or associations with fetal exposure to ASMs (-2.6 [-11.0 to 5.7], p = 0.530). Secondary analyses revealed fetal exposure-dependent effects for executive function in children of WWE (7.0 [2.9-11.2], p = 0.001), which are most marked for levetiracetam (12.9 [4.2-21.6], p = 0.004). Our findings suggest that even for relatively safe ASMs, dosing needs to be adjusted to concentrations that prevent seizures, but balance risks to the fetus that high concentrations may pose. TRIAL REGISTRATION INFORMATION: The study is registered at ClinicalTrials.gov as NCT01730170.

Antiseizure adverse drug reaction and associated factors among epileptic patients at Jimma Medical Center: a prospective observational study.

A growing body of evidence suggests that adverse drug reactions (ADRs) are a major cause of morbidity and mortality in the healthcare system. Fifteen to twenty-five percent of patients with epilepsy discontinued antiseizure drugs (ASDs) within 6 months of therapy owing to intolerable adverse drug reactions. In Ethiopia, the prevalence of antiseizure adverse drug reactions and associated factors was not extensively conducted in advanced settings like Jimma Medical Centers. Hence, the objective of this study is to assess patterns of adverse drug reactions and associated factors among ambulatory epileptic patients at tertiary hospitals in Ethiopia. A hospital-based prospective observational study was spanned for 1 year. Two hundred ninety patients were consecutively recruited into the study from all epileptic patients attending the ambulatory clinic. Relevant data were collected through patient interviews and medical chart reviews. The causality assessment was done by using the Naranjo Probability Scale. Epi-Data manager version 4.6.0.4 was used for data entry and statistical analysis was performed by Statistical Package for Social Science version 25.0 (SPSS). Stepwise backward logistic regression analysis was done to identify factors that increase the risk of antiseizure adverse drug reactions. The mean (± SD) age of the participants were 29.91(± 11.26) years. The overall prevalence of ADR was 33.8% (95% CI 29.2-39.9%). A total of 110 adverse drug reactions were identified among 98 patients with an average of 1.12 per patient. ADRs were frequently reported with phenobarbital (52.04%) and phenytoin (34.70%). The commonly identified adverse drug reactions were epigastric pain (27.55%) and central nervous system drowsiness (23.46%). Comorbidity (AOR = 5.91, 95% CI (2.14-16.32), seizure-free period of fewer than 2 years (AOR = 1.94, 95% CI (1.18-3.19), and polytherapy (AOR = 1.35, 95% CI (1.80-2.26) were significantly associated with adverse drug reactions. This trial had a comparatively high percentage of adverse medication reactions. Adverse medication reactions were more common in patients with polytherapy, comorbidities, and seizure-free durations less than two years. Therefore, medical practitioners should advise patients who exhibit these traits on how to reduce or avoid bad drug responses or provide comfort in the event of small incidents.

Psychiatric implications of anti-seizure medications in epileptic population.

BACKGROUND AND OBJECTIVE: Epilepsy is a prevalent neurological disorder that affects a significant number of individuals globally. This condition is associated with a high occurrence of psychiatric comorbidities, which can significantly affect the quality of life of individuals affected. The aim of this study was to investigate the association between antiseizure therapies and the likelihood of psychiatric comorbidities in individuals with epilepsy. METHODOLOGY: Data for this study was gathered from the Neurology referral center in Islamabad, Pakistan. A standardized questionnaire was utilized to gather data from 120 individuals diagnosed with epilepsy. The survey consisted of inquiries regarding the management of seizures, the utilization of anti-seizure medications, and the presence of psychiatric comorbidities. The data was analyzed using the Statistical Package for the Social Sciences (SPSS). RESULTS: The findings indicated that individuals who were using multiple antiseizure medications had a notably higher likelihood of having psychiatric comorbidities in comparison to those who were on mono therapy (p = 0.010). suggests that patients with unsuccessful seizure control are more probable to have psychiatric comorbidities as compared to those with good seizure control (p = 0.029). CONCLUSION: To conclude poor seizure control and poly therapy are associated with increased risk of psychiatric comorbidities.

Continuous spike-wave of slow sleep in a patient with KCNB1-related epilepsy responsive to highly purified cannabidiol: a case report and comparison with literature.

KCNB1-associated encephalopathy is characterized by intellectual disability (ID), autism spectrum disorder and epilepsy. Specific treatments are still lacking. We describe a 12-year-old boy with severe ID and treatment-resistant seizures due to a pathogenic KCNB1 variant. His EEG showed a CSWS pattern. Aged 11, he started treatment with highly purified cannabidiol (CBD) and has been seizure free for 18 months, with significant EEG and social skills improvements. This suggests CBD may benefit CSWS, likely due to its anti-inflammatory properties. Some preclinical studies also indicate CBDs interact with voltage-gated channels, leading us to speculate its possible role for treating KCNB1 related encephalopathy.

Re-evaluating the placebo response in recent canine dietary epilepsy trials.

The placebo response is a common phenomenon. Limited evidence is available about its magnitude in canine epilepsy trials, even though it can significantly influence the efficacy evaluation of new treatments. It was hypothesised that the placebo response is diminished when epilepsy trials are conducted in a prospective crossover design. Seizure data spanning six months from three previous multicenter epilepsy studies were analysed. The monthly seizure frequency of 60 dogs diagnosed with idiopathic epilepsy was calculated, comparing baseline data with placebo treatment. Furthermore, differentiation was made between dogs randomised to the placebo group early (Phase 1: first 3 months) or later during the study (Phase 2: second 3 months).The analysis did not reveal any placebo response in terms of monthly seizure frequency. Instead, an increase was noted during the placebo treatment period, with a mean of 2.95 seizures per month compared to 2.30 seizures per month before study entry (p = 0.0378). Additionally, a notable phase effect was observed. Dogs receiving the placebo in the second study phase exhibited a significant increase in monthly seizure frequency compared to baseline (p = 0.0036). Conversely, no significant difference from baseline was observed for dogs receiving the placebo in the first study phase. These findings underscore the considerable variability in placebo responses observed in trials for canine epilepsy, contrasting with previous limited data. The identified phase effect should be carefully considered in the design and evaluation of canine epilepsy trials to ensure a more accurate assessment of efficacy for new treatments.

Structural connectivity as a predictive factor for perampanel response in patients with epilepsy.

OBJECTIVES: This study aimed to identify clinical characteristics that could predict the response to perampanel (PER) and determine whether structural connectivity is a predictive factor. METHODS: We enrolled patients with epilepsy who received PER and were followed-up for a minimum of 12 months. Good PER responders, who were seizure-free or presented with more than 50 % seizure reduction, were classified separately from poor PER responders who had seizure reduction of less than 50 % or non-responders. A graph theoretical analysis was conducted based on diffusion tensor imaging to calculate network measures of structural connectivity among patients with epilepsy. RESULTS: 106 patients with epilepsy were enrolled, including 26 good PER responders and 80 poor PER responders. Good PER responders used fewer anti-seizure medications before PER administration compared to those by poor PER responders (3 vs. 4; p = 0.042). Early PER treatment was more common in good PER responders than poor PER responders (46.2 vs. 21.3 %, p = 0.014). Regarding cortical structural connectivity, the global efficiency was higher and characteristic path length was lower in good PER responders than in poor PER responders (0.647 vs. 0.635, p = 0.006; 1.726 vs. 1,759, p = 0.008, respectively). For subcortical structural connectivity, the mean clustering coefficient and small-worldness index were higher in good PER responders than in poor PER responders (0.821 vs. 0.791, p = 0.009; 0.597 vs. 0.560, p = 0.009, respectively). CONCLUSION: This study demonstrated that early PER administration can predict a good PER response in patients with epilepsy, and structural connectivity could potentially offer clinical utility in predicting PER response.