Seizure-free Group Research Articles

Epileptogenic network of focal epilepsies mapped with cortico-cortical evoked potentials

ObjectiveThe goal of this study was to investigate the spatial extent and functional organization of the epileptogenic network through cortico-cortical evoked potentials (CCEPs) in patients being evaluated with intracranial stereoelectroencephalography. MethodsWe retrospectively included 25 patients. We divided the recorded sites into three regions: epileptogenic zone (EZ); propagation zone (PZ); and noninvolved zone (NIZ). The root mean square of the amplitudes was calculated to reconstruct effective connectivity network. We also analyzed the N1/N2 amplitudes to explore the responsiveness influenced by epileptogenicity. Prognostic analysis was performed by comparing intra-region and inter-region connectivity between seizure-free and non-seizure-free groups. ResultsOur results confirmed that stimulation of the EZ caused the strongest responses on other sites within and outside the EZ. Moreover, we found a hierarchical connectivity pattern showing the highest connectivity strength within EZ, and decreasing connectivity gradient from EZ, PZ to NIZ. Prognostic analysis indicated a stronger intra-EZ connection in the seizure-free group. ConclusionThe EZ showed highest excitability and dominantly influenced other regions. Quantitative CCEPs can be useful in mapping epileptic networks and predicting surgical outcome. SignificanceThe generated computational connectivity model may enhance our understanding of epileptogenic networks and provide useful information for surgical planning and prognosis prediction.

Response to antiepileptic drugs after unsuccessful epilepsy surgery: A multivariate analysis of 103 patients

ObjectEpilepsy patients may still have seizures after surgery, and there have been few studies on the response to antiepileptic drugs (AEDs) after surgery failure. The purpose of this study was to analyze the response to AEDs after unsuccessful epilepsy surgery. MethodsPatients who underwent unsuccessful epilepsy surgery between January 1999 and January 2019 were evaluated. Patient demographics, etiology, factors related to surgery and AED use patterns were assessed. ResultsAfter excluding the 5 patients who were lost to follow-up and the 2 patients who died, the records of 103 consecutive patients were analyzed. Ninety patients (87.4 %) had seizure recurrence within one year after surgery, 2 (1.9 %) patients had recurrence from one year to two years after surgery, and 11 (10.7 %) patients had recurrence two or more years after surgery (2–10 years). After surgery failure, the patients tried at least 2 kinds of AEDs with different mechanisms for more than 2 years. The average total number of AEDs used was 5.97, the average number of AEDs used before surgery was 3.21, and the average number of AEDs used after surgery was 4.02. After retreatment with AEDs, 10 patients (9.7 %) were seizure-free, 18 patients’ (17.5 %) seizures were alleviated, and 75 patients (72.8 %) had seizures as they did prior to the adjustments. The number of AEDs used before and after surgery and the total number of AEDs were not significantly different among the seizure free group, alleviated seizure group and no change group. There were no significant differences in seizure onset age, surgery age, etiology, time between seizure onset and surgery, magnetic resonance imaging, seizure type, localization and lateralization of the surgery site among the three groups. ConclusionsThe results showed that a small percentage of patients (27.2 %) who undergo unsuccessful epilepsy surgery benefit from AED adjustments; however, the vast majority of patients (72.8 %) do not benefit from AED adjustments.

Investigation of poststroke epilepsy (INPOSE) study: a multicenter prospective study for prediction of poststroke epilepsy.

Poststroke epilepsy is a common problem in clinical practice. This study aimed to determine the predictors of poststroke epilepsy and to identify the risk factors. A total of 436 patients were enrolled for this study. Baseline characteristics were recorded. Patients were followed up for 3years. According to the occurrence of late seizures (i.e., seizure occurring 8days or later after the stroke), the patients were separated into two groups: a seizure group and a seizure-free group. Baseline characteristics were compared between the groups. Univariate and multivariate Cox regression analysis was used to identify the risk factors for occurrence of poststroke epilepsy. The study was registered in the University Hospital Medical Information Network Center Clinical Trials Registry (registration number UMIN000009659, date 28/December/2012). Among the 436 patients, 26 developed late seizures-an incidence rate of 5.96%. In univariate analysis, female, subarachnoid hemorrhage, hemorrhagic lesion, lesion affecting the cortex, lesion affecting the frontal lobe, and absence of comorbidities were the significant risk factors for occurrence of epilepsy. In multivariate analysis, the independent predictors of poststroke epilepsy were hemorrhagic lesion (hazard ratio (HR) = 3.03) and lesion location in the cortex (HR = 4.64). The incidence of poststroke epilepsy in patients with both two risk factors was 15.4%. Poststroke epilepsy occurs in almost 6% of patients within 3years after stroke onset. Hemorrhagic stroke and subcortical lesion appear to be significantly associated with likelihood of developing epilepsy. Thus, prophylactic administration of antiepileptic drugs could be useful for stroke patients with these two risk factors.

Social functioning and health-related quality of life trajectories in people with epilepsy after epilepsy surgery

ObjectiveAn improvement in quality of life (QoL) over time after epilepsy surgery has been demonstrated in people with epilepsy; however, social functioning has been less investigated. We conducted this study to examine whether postsurgical improvement is parallel between QoL and social functioning in patients with epilepsy. MethodsWe retrospectively reviewed patients who underwent epilepsy surgery. All participants completed a comprehensive neuropsychological assessment, the Quality of Life in Epilepsy Inventory (QOLIE-89) questionnaire, and the Social and Occupational Functioning Scale for Epilepsy (SOFSE) before surgery and at 3 months, 6 months, and 1 year after surgery. Demographic and epilepsy-related information was also collected. Generalized estimating equations with identity links were used to model the QOLIE-89 and SOFSE over time and possible associated factors. A p < 0.05 was considered statistically significant. ResultsA total of 76 patients, including 36 males and 43 females aged 18 to 62 years were collected. Both total QOLIE-89 and overall SOFSE improved over time after epilepsy surgery (adjusted p value < 0.001 and 0.002, respectively, with Bonferroni's correction). Total QOLIE-89 improved 3 months after surgery, while overall SOFSE showed no significant improvement until 6 months after surgery. The presurgical Full-Scale Intelligence Quotient (FSIQ) of the Wechsler Adult Intelligence Scale-III and years of education were significantly associated with time-dependent improvement for both total QOLIE-89 and overall SOFSE (p value < 0.001). At one year after surgery, overall SOFSE and total QOLIE-89 scores were significantly higher in the seizure-free group than in the nonseizure-free group (p value = 0.040 and 0.032, respectively). ConclusionSocial functioning significantly improved in people with epilepsy after surgery as QoL, but it took more time to exhibit improvement. People with better FSIQ and more years of education had better improvement in social functioning over time. The early intervention of rehabilitation programs after epilepsy surgery might be necessary to facilitate the improvement in social functioning.

Localization value of subclinical seizures on scalp video-EEG in epilepsy presurgical evaluation.

To evaluate the localization value and prognostic significance of subclinical seizures (SCSs) on scalp video-electroencephalography monitoring (VEEG) in comparison to clinical seizures (CSs) in patients who had epilepsy surgery. We included 123 consecutive patients who had SCSs and CSs during scalp-VEEG evaluation. All patients had subsequent epilepsy surgery and at least 1-year follow-up. Concordance between SCSs and CSs was summarized into five categories: complete, partial, overlapping, no concordance, or indeterminate. Using the same scheme, we analyzed the relationship between resection and SCS/CS localizations. The concordance measures, along with demographic, electroclinical, and other presurgical evaluation data, were evaluated for their associations with postoperative seizure outcome. Sixty-nine patients (56.1%) had seizure-free outcome at 1-year follow-up. In 68 patients (55.3%), the localizations of SCSs and CSs were completely concordant. Multivariate logistic analysis showed that complete SCS/CS concordance was independently associated with seizure-free outcome at 1-year (P=.020) and 2-year follow-up (P=.040). In the temporal lobe epilepsy (TLE) seizure-free group, SCS localization was completelycontained within the resection in 44.4% andCS localization was completelycontained within the resection in41.7%; in the extratemporal lobe epilepsy (ETLE) seizure-free group, SCS localization was completelycontained within the resection in 54.5%and CS localization was completely contained within the resection in57.6%. Complete concordance between CS and SCS localization is a positive prognostic factor for 1-year and 2-year postoperative seizure-free outcome. Localization value of SCSs on scalp VEEG is similar to that of CSs for TLE and ETLE. Although SCSs cannot replace CSs, localization information from SCSs should not be ignored.

Learning to define an electrical biomarker of the epileptogenic zone.

The role of fast activity as a potential biomarker in localization of the epileptogenic zone (EZ) remains controversial due to recently reported unsatisfactory performance. We recently identified a “fingerprint” of the EZ as a time‐frequency pattern that is defined by a combination of preictal spike(s), fast oscillatory activity, and concurrent suppression of lower frequencies. Here we examine the generalizability of the fingerprint in application to an independent series of patients (11 seizure‐free and 13 non‐seizure‐free after surgery) and show that the fingerprint can also be identified in seizures with lower frequency (such as beta) oscillatory activity. In the seizure‐free group, only 5 of 47 identified EZ contacts were outside the resection. In contrast, in the non‐seizure‐free group, 104 of 142 identified EZ contacts were outside the resection. We integrated the fingerprint prediction with the subject's MR images, thus providing individualized anatomical estimates of the EZ. We show that these fingerprint‐based estimates in seizure‐free patients are almost always inside the resection. On the other hand, for a large fraction of the nonseizure‐free patients the estimated EZ was not well localized and was partially or completely outside the resection, which may explain surgical failure in such cases. We also show that when mapping fast activity alone onto MR images, the EZ was often over‐estimated, indicating a reduced discriminative ability for fast activity relative to the full fingerprint for localization of the EZ.

Epileptogenicity and surgical outcome in post stroke drug resistant epilepsy in children and adults

OBJECTIVE Post-stroke epilepsy (PSE) represents a rare etiology in patients undergoing pre-surgical evaluation for epilepsy. Refractory PSE has been traditionally surgically treated with hemispherotomy. The aim of this study was to define the electrophysiological features of epileptogenic zone (EZ) using stereoelectroencephalography (SEEG) recordings in patients with refractory PSE. METHODS We analyzed ictal SEEG recordings from 21 consecutive patients. Epileptogenicity was quantified using the “epileptogenicity index” (EI) method in distant and perilesional cortical structures. We identified different seizure onset patterns (SOP) through a visual and time-frequency analysis. RESULTS We found that 81% of patients showed a complex organization of EZ, involving remote and perilesional structures. EZ involved a significantly (p < 0.01) higher number of distant regions displaying a high epileptogenicity (EI ≥ 0.3). Low voltage fast activity (LFA) and high amplitude slow activity (HAS) patterns were observed respectively in 85.7% and 14.3% of patients. Surgery was proposed in 12/21 patients. Good surgical outcome (Engel Class I or II) was observed for all patients who underwent tailored functional disconnection based on SEEG results. Shorter epilepsy duration to surgery was found in the seizure-free group. SIGNIFICANCE Refractory PSE may present a complex organization of EZ. SEEG recordings are warranted to guide tailored hemispherectomy.

Leukocyte expression profiles reveal gene sets with prognostic value for seizure-free outcome following stereotactic laser amygdalohippocampotomy

Among patients with intractable epilepsy, the most commonly performed surgical procedure is craniotomy for amygdalohippocampectomy (AH). Stereotactic laser amygdalohippocampotomy (SLAH) has also been recently employed as a minimally invasive treatment for intractable temporal lobe epilepsy (TLE). Among patients treated with AH and SLAH approximately 65% and 54% of patients become seizure-free, respectively. Therefore, selection criteria for surgical candidates with improved prognostic value for post-operative seizure-free outcome are greatly needed. In this study, we perform RNA sequencing (RNA-Seq) on whole blood leukocyte samples taken from 16 patients with intractable TLE prior to SLAH to test the hypothesis that pre-operative leukocyte RNA expression profiles are prognostic for post-operative seizure outcome. Multidimensional scaling analysis of the RNA expression data indicated separate clustering of patients with seizure free (SF) and non-seizure-free (NSF) outcomes. Differential expression (DE) analysis performed on SF versus NSF groups revealed 24 significantly differentially expressed genes (≥2.0-fold change, p-value < 0.05, FDR <0.05). Network and pathway analyses identified differential activation of pathways involved in lipid metabolism, morphology of oligodendrocytes, inflammatory response, and development of astrocytes. These results suggest that pre-operative leukocyte expression profiles have prognostic value for seizure outcome following SLAH.

Long-term outcome of seizure-free patients and risk factors of relapse following antiepileptic drug withdrawal

ObjectiveThis study aimed to investigate the long-term outcome in seizure-free patients and to explore the risk factors of seizure relapse following antiepileptic drug (AED) withdrawal. MethodsThis study included 161 patients who had been seizure-free for at least 2 years. These patients were monitored over a follow-up period of at least 3 years or until seizure relapse after AED withdrawal. Patients were grouped into a seizure-free group and a relapse group. Risk factors of seizure relapse were analyzed. ResultsDuring the follow-up period, 72 patients (44.7%) relapsed while 89 patients (55.3%) did not. The average time of relapse was 19.12 ± 27.17 months after the initiation of AED withdrawal, and majority of cases occurred within the first 24 months of AED withdrawal (73.6%). Univariate analysis showed that the likelihood of relapse was higher in patients with uncontrolled seizures beyond the first 6 months of AED therapy initiation, patients with a history of perinatal injury, patients with multiple seizure types, and patients who had been treated with a combination of AEDs. Multiple logistic regression analysis revealed that uncontrolled seizures beyond the first 6 months of AED treatment and a history of perinatal injury were independent risk factors of seizure relapse. ConclusionIn the majority of cases, epilepsy relapse occurred within the first two years after the initiation of AED withdrawal. The independent risk factors of seizure relapse were uncontrolled seizures beyond the first 6 months of AED therapy and cases with a history of perinatal injury.

Cognition, health-related quality of life, and mood in children and young adults diagnosed with a glioneuronal tumor in childhood

AimsThe aim of this study was to investigate long-term cognitive outcome, health-related quality of life (HRQoL), and psychiatric symptoms in children and young adults diagnosed with a glioneuronal tumor in childhood. MethodsTwenty-eight children and adolescents (0–17.99years) with a minimum postoperative follow-up time of five years were eligible for the study; four persons declined participation. A cross-sectional long-term follow-up evaluation was performed using the following study measures: Wechsler Intelligence Scale for Children (WISC-IV) or Wechsler Adult Intelligence Scale (WAIS-IV), Reys Complex Figure Test (RCFT), Short Form 36 version 2 (SF-36v2), Short Form 10 (SF-10), Quality of Life in Epilepsy 31 (QOLIE-31), Hospital Anxiety Depression Scale (HADS) or Beck Youth Inventory Scales (BYI), and Rosenberg Self-Esteem Scale. Historical WISC-III and RCFT data were used to compare cognitive longitudinal data. ResultsMean follow-up time after surgery was 12.1years. Sixty-three percent (15/24) were seizure-free. Despite a successive postoperative gain in cognitive function, a significant reduction relative to norms was seen in the seizure-free group with respect to perceptual reasoning index (PRI), working memory index (WMI), and full-scale intelligence quotient (FSIQ). Seizure freedom resulted in acceptable HRQoL. Thirty-two percent and 16% exceeded the threshold level of possible anxiety and depression, respectively, despite seizure freedom. ConclusionAlthough lower than in corresponding reference groups, cognitive outcome and HRQoL are good provided that seizure freedom or at least a low seizure severity can be achieved. There is a risk of elevated levels of psychiatric symptoms. Long-term clinical follow-up is advisable.

Magnetoencephalographic Spike Analysis in Patients With Focal Cortical Dysplasia: What Defines a “Dipole Cluster”?

BackgroundThe purpose of this study is to clarify the source distribution patterns of magnetoencephalographic spikes correlated with postsurgical seizure-free outcome in pediatric patients with focal cortical dysplasia. Patients and methodsThirty-two patients with pathologically confirmed focal cortical dysplasia were divided into seizure-free and seizure-persistent groups according to their surgical outcomes based on Engel classification. In each patient, presurgical magnetoencephalography was reviewed. Dipole sources of magnetoencephalographic spikes were calculated according to a single dipole model. We obtained the following quantitative indices for evaluating dipole distribution: maximum distance over all pairs of dipoles, standard deviation of the distances between each dipole and the mean coordinate of all dipoles, average nearest neighbor distance, the rate of dipoles located within 10, 20, and 30 mm from the mean coordinate, and the rate of dipoles included in the resection. These indices were compared between the two patient groups. ResultsAverage nearest neighbor distance was significantly smaller in the seizure-free group than in the seizure-persistent group (P = 0.008). The rates of dipoles located within 10, 20, and 30 mm from the mean coordinate were significantly higher in the seizure-free group (P = 0.001, 0.001, 0.005, respectively). The maximum distance, standard deviation, and resection rate of dipoles did not show a significant difference between the two groups. ConclusionsA spatially restricted dipole distribution of magnetoencephalographic spikes is correlated with postsurgical seizure-free outcomes in patients with focal cortical dysplasia. The distribution can be assessed by quantitative indices that are clinically useful in the presurgical evaluation of these patients.

Postoperative seizure outcome-guided machine learning for interictal electrocorticography in neocortical epilepsy.

The objective of this study was to introduce a new machine learning guided by outcome of resective epilepsy surgery defined as the presence/absence of seizures to improve data mining for interictal pathological activities in neocortical epilepsy. Electrocorticographies for 39 patients with medically intractable neocortical epilepsy were analyzed. We separately analyzed 38 frequencies from 0.9 to 800 Hz including both high-frequency activities and low-frequency activities to select bands related to seizure outcome. An automatic detector using amplitude-duration-number thresholds was used. Interictal electrocorticography data sets of 8 min for each patient were selected. In the first training data set of 20 patients, the automatic detector was optimized to best differentiate the seizure-free group from not-seizure-free-group based on ranks of resection percentages of activities detected using a genetic algorithm. The optimization was validated in a different data set of 19 patients. There were 16 (41%) seizure-free patients. The mean follow-up duration was 21 ± 11 mo (range, 13-44 mo). After validation, frequencies significantly related to seizure outcome were 5.8, 8.4-25, 30, 36, 52, and 75 among low-frequency activities and 108 and 800 Hz among high-frequency activities. Resection for 5.8, 8.4-25, 108, and 800 Hz activities consistently improved seizure outcome. Resection effects of 17-36, 52, and 75 Hz activities on seizure outcome were variable according to thresholds. We developed and validated an automated detector for monitoring interictal pathological and inhibitory/physiological activities in neocortical epilepsy using a data-driven approach through outcome-guided machine learning. NEW & NOTEWORTHY Outcome-guided machine learning based on seizure outcome was used to improve detections for interictal electrocorticographic low- and high-frequency activities. This method resulted in better separation of seizure outcome groups than others reported in the literature. The automatic detector can be trained without human intervention and no prior information. It is based only on objective seizure outcome data without relying on an expert's manual annotations. Using the method, we could find and characterize pathological and inhibitory activities.

Mammillary body changes and seizure outcome after laser interstitial thermal therapy of the mesial temporal lobe

ObjectiveThe mammillary bodies have long been known as the primary relay center for the hippocampus. The fornix is the primary efferent pathway of the hippocampus, with its postcommissural fibers terminating in the mammillary bodies. In this study, we describe change in mammillary body volume after laser interstitial thermal therapy (LiTT) for mesial temporal lobe epilepsy and correlate it with seizure outcome. MethodsPre- and post-LiTT ablation magnetic resonance imaging was reviewed in axial and coronal planes to determine mammillary body volume as calculated by the ellipsoid method. Patient demographics, clinical semiology, and seizure localization were analyzed. The primary end-point was seizure freedom at 1 year after LiTT. The change in the size of the mammillary body were correlated with the postoperative seizure freedom at 1 year using the Wilcoxon/Kruskal-Wallis test for statistical significance. ResultsBetween December 1, 2012 and June 1, 2015, 22 patients underwent LiTT for mesial temporal lobe epilepsy. Two patients were excluded due to lack of follow-up. Of the remaining 20 patients, 13 were seizure free at 1 year. In the seizure free group, there was an average 34.6% (± 13%) decline in ipsilateral mammillary body volume, as opposed to an average decline of 8.4% (± 10.9%) in patients with continued seizures (P = 0.0026). ConclusionsOur findings show a statistically significant correlation between postoperative volume reduction in ipsilateral mammillary body and seizure outcomes after LiTT. With further validation, this finding could be a useful marker of adequacy of ablation independent of ablation volumes and determinant of potential benefit of additional surgical intervention in patients with poor outcomes after LiTT.

Impact of sleep disorders on the risk of seizure recurrence in juvenile myoclonic epilepsy

ObjectiveThe aim of this study was to investigate the presence of sleep disturbances in patients with juvenile myoclonic epilepsy (JME) using sleep questionnaires. Further, we tried to evaluate whether alterations in sleep quality may influence the clinical expression of JME. MethodsSixty-two patients with JME treated with levetiracetam were included. Demographic and clinical variables were collected. Moreover, all patients submitted the Pittsburgh Sleep Quality index (PSQI) and the Epworth Sleepiness Scale (ESS) in order to respectively assess sleep quality during the last month and daytime sleepiness. All patients were followed up for a 6-month period and divided in two groups: seizure-free (Group 1) and seizure recurrence (Group 2). The PSQI and ESS scores were synthesized as binary variables <5/≥5 and <10/≥10, respectively. A comprehensive analysis was performed to evaluate the independent effect of the sleep quality and daytime sleepiness on the risk of having seizures during the follow-up. ResultsBoth reduced sleep quality during the last month and daytime sleepiness were associated with an increased risk of suffering from seizures during the follow-up period. In fact, a PSQI score<5 or an ESS score<10 resulted significantly associated with the absence of seizure recurrence (p<0.004 and p<0.001, respectively). Increasing age had a significantly protective effect in the risk of seizure relapse. ConclusionsOur findings show that reduced sleep quality and daytime sleepiness in patients with JME increase the risk of seizure occurrence in spite of an appropriate pharmacological treatment. This negative effect seems to be more relevant in younger patients. Sleep disorders and their specific correction should be taken into consideration for the management of patients with JME.

Outcome of epilepsy in patients with mitochondrial disorders: Phenotype genotype and magnetic resonance imaging correlations

ObjectivesStudies exploring the outcome of epilepsy in patients with mitochondrial disorders are limited. This study examined the outcome of epilepsy in patients with mitochondrial disorders and its relation with the clinical phenotype, genotype and magnetic resonance imaging findings. Patients and methodsThe cohort was derived from the database of 67 patients with definite genetic diagnosis of mitochondrial disorders evaluated over a period of 11years (2006–2016). Among this, 27 had epilepsy and were included in final analysis. Data were analyzed with special reference to clinical phenotypes, genotypes, epilepsy characteristics, EEG findings, anti epileptic drugs used, therapeutic response, and magnetic resonance imaging findings. Patients were divided into three groups according to the seizure frequency at the time of last follow up: Group I- Seizure free; Group II- Infrequent seizures; Group III- uncontrolled seizures. For each group the clinical phenotype, genotype, magnetic resonance imaging and duration of epilepsy were compared. ResultsThe phenotypes & genotypes included Mitochondrial Encephalopathy Lactic Acidosis and Stroke like episodes (MELAS) & m.3243A>G mutation (n = 10), Myoclonic Epilepsy Ragged Red Fiber syndrome (MERRF) & m.8344A>G mutation (n = 4), Chronic Progressive External Ophthalmoplegia plus &POLG1 mutation (CPEO, n = 6), episodic neuroregression due to nuclear mutations (n = 6; NDUFV1 (n = 3), NDUFA1, NDUFS2, MPV17-1 one each), and one patient with infantile basal ganglia stroke syndrome, mineralizing angiopathy &MT-ND5 mutations. Seven patients (25.9%) were seizure free; seven had infrequent seizures (25.9%), while thirteen (48.1%) had frequent uncontrolled seizures. Majority of the subjects in seizure free group had episodic neuroregression & leukoencephalopathy due to nuclear mutations (85.7%). Patients in group II with infrequent seizures had CPEO, POLG1 mutation and a normal MRI (71%) while 62% of the subjects in group III had MELAS, m.3243A>G mutation and stroke like lesions on MRI. ConclusionsA fair correlation exists between the outcome of epilepsy, clinical phenotypes, genotypes and magnetic resonance imaging findings in patients with mitochondrial disorders. The recognition of these patterns is important clinically because of the therapeutic and prognostic implications.

Seizure and cognitive outcomes after resection of glioneuronal tumors in children.

Glioneuronal tumors (GNTs) are well-recognized causes of chronic drug-resistant focal epilepsy in children. Our practice involves an initial period of radiological surveillance and antiepileptic medications, with surgery being reserved for those with radiological progression or refractory seizures. We planned to analyze the group of patients with low-grade GNTs, aiming to identify factors affecting seizure and cognitive outcomes. We retrospectively reviewed the medical records of 150 children presenting to Great Ormond Street Hospital with seizures secondary to GNTs. Analysis of clinical, neuroimaging, neuropsychological, and surgical factors was performed to determine predictors of outcome. Seizure outcome at final follow-up was classified as either seizure-free (group A) or not seizure-free (group B) for patients with at least 12-months follow-up postsurgery. Full-scale intelligence quotient (FSIQ) was used as a measure of cognitive outcome. Eighty-six males and 64 females were identified. Median presurgical FSIQ was 81. One hundred twenty-one patients (80.5%) underwent surgery. Median follow-up after surgery was 2years, with 92 patients (76%) having at least 12months of follow-up after surgery. Seventy-four patients (80%) were seizure-free, and 18 (20%) continued to have seizures. Radiologically demonstrated complete tumor resection was associated with higher rates of seizure freedom (P=.026). Higher presurgical FSIQ was related to shorter epilepsy duration until surgery (P=.012) and to older age at seizure onset (P=.043). A high proportion of children who present with epilepsy and GNTs go on to have surgical tumor resection with excellent postoperative seizure control. Complete resection is associated with a higher chance of seizure freedom. Higher presurgical cognitive functioning is associated with shorter duration of epilepsy prior to surgery and with older age at seizure onset. Given the high rate of eventual surgery, early surgical intervention should be considered in children with continuing seizures associated with GNTs.

Younger age at surgery and lesser seizure frequency as prognostic factors for favorable seizure-related outcome after glioma resection in adults.

The identification of variables predictive of good seizure control following surgical tumor resection in adult glioma patients with tumor-related epilepsy would greatly benefit treatment decisions. Therefore, we analyzed the clinical data of adult patients with tumor-related epilepsy who underwent tumor resection at our institute between November 2011 and August 2013. Patients were divided into seizure-free (Engel Ia) and unfavorable outcome groups (Engel Ib–IV), and potential prognostic factors were analyzed. Of 90 patients, 61 (68%) had a favorable outcome at an average of 3 years after surgery. Our analyses indicated that younger age at surgery (P=0.048) and rare seizure frequency (P=0.006) were associated with significantly more favorable postoperative seizure-related outcomes. In conclusion, younger age at surgery and lesser seizure frequency were independent predictors of favorable epileptic seizure control after glioma resection in adults. Thus, early surgical resection is necessary for achieving favorable seizure outcome.

Correlation between prescribed daily dose, seizure freedom and defined daily dose in antiepileptic drug treatment.

Background Although defined daily doses (DDD) for antiepileptic drugs (AED) have been assigned only in combination therapy, based on the literature, most patients take them in monotherapy. Furthermore, discrepancies between DDD and prescribed daily dose (PDD) were observed. Objective First, to determine PDDs of AEDs and to reveal PDD/DDD ratio among seizure free versus not seizure free patients in everyday clinical practice. Second, to test the applicability of 75% cut-off of DDD to achieve seizure freedom. Furthermore, to find out what factors might influence PDD. Setting Outpatient data files at a Hungarian university hospital were studied. Methods A retrospective, 20-year cross-sectional database was compiled from 1282 epileptic outpatients' files. Main outcome measure Seizure freedom and PDD were used as outcome measures. Results The mean DDD% of all prescribed AEDs increased steadily from monotherapy, through bitherapy towards polytherapy (p<0.0001). Most seizure free patients took AEDs in doses in the range of ≤75% of DDDs in monotherapy and bitherapy. Older AEDs (carbamazepine and valproate) were given in a significantly higher mean dose in bitherapy in the seizure free group. Among the newer types, only levetiracetam and lamotrigine had a significantly higher DDD% in mono-, bi-, and polytherapy. Confirmed by logistic regression analysis, gender, age, type of epilepsy, and number of AEDs had a significant impact on the value of 75% DDD. Conclusion No significant unfavourable impact of the lower ratio of PDD/DDD on the outcome of achieving seizure freedom has been confirmed. As a measure of seizure freedom, 75% of DDD may be used, although individual therapy must be emphasised. Precisely quantified DDD would provide a more accurate calculation of other derived values.

Population pharmacokinetics and dose-response relationship of levetiracetam in adult patients with epilepsy

Levetiracetam (LEV) is commonly used as a mono- or adjunctive therapy for treating patients with partial and generalized epilepsy. This study aimed to develop a population pharmacokinetic (PK) model of LEV, based on sparse data, and to explore LEV efficacy relative to its PK properties in patients with epilepsy. We included 483 LEV concentrations from 425 patients with epilepsy that received multiple oral LEV doses. We performed a population PK analysis, implemented in NONMEM (version 7.2). In addition, we explored the relationships between seizure control and PK variables (i.e., LEV dose, trough concentration, and the number of concomitant anti-epileptic drugs). LEV concentration–time profiles were adequately described with a one-compartment, open linear model, with first-order absorption, and additive residual error. The typical population estimates of the apparent clearance (CL/F) and the volume of distribution (V/F) were 3.9L/h and 65.3L, respectively. Body weight was a significant covariate for CL/F and V/F; the estimated glomerular filtration rate only significantly affected CL/F; and concomitant intake of other anti-epileptic drugs did not significantly affect either parameter. A cumulative percentage analysis revealed that over 95% of patients that remained seizure-free received LEV doses of 2000mg/day or lower. LEV trough concentrations were not significantly different between seizure-free and seizure groups, for each LEV dose. In conclusion, we successfully developed a population PK model of LEV, which enabled investigation of LEV efficacy, relative to its PK properties. The findings in this study can be utilized to optimize LEV dosing regimens in clinical practice.

Integrating opioid overdose prevention in the emergency department

The aim of this study was to investigate long-term cognitive outcome, health-related quality of life (HRQoL), and psychiatric symptoms in children and young adults diagnosed with a glioneuronal tumor in childhood.Twenty-eight children and adolescents (0–17.99 years) with a minimum postoperative follow-up time of five years were eligible for the study; four persons declined participation. A cross-sectional long-term follow-up evaluation was performed using the following study measures: Wechsler Intelligence Scale for Children (WISC-IV) or Wechsler Adult Intelligence Scale (WAIS-IV), Reys Complex Figure Test (RCFT), Short Form 36 version 2 (SF-36v2), Short Form 10 (SF-10), Quality of Life in Epilepsy 31 (QOLIE-31), Hospital Anxiety Depression Scale (HADS) or Beck Youth Inventory Scales (BYI), and Rosenberg Self-Esteem Scale. Historical WISC-III and RCFT data were used to compare cognitive longitudinal data.Mean follow-up time after surgery was 12.1 years. Sixty-three percent (15/24) were seizure-free. Despite a successive postoperative gain in cognitive function, a significant reduction relative to norms was seen in the seizure-free group with respect to perceptual reasoning index (PRI), working memory index (WMI), and full-scale intelligence quotient (FSIQ). Seizure freedom resulted in acceptable HRQoL. Thirty-two percent and 16% exceeded the threshold level of possible anxiety and depression, respectively, despite seizure freedom.Although lower than in corresponding reference groups, cognitive outcome and HRQoL are good provided that seizure freedom or at least a low seizure severity can be achieved. There is a risk of elevated levels of psychiatric symptoms. Long-term clinical follow-up is advisable.