Achieve Seizure Control Research Articles

Efficacy and safety of perampanel in patients with drug-resistant partial seizures after conversion from double-blind placebo to open-label perampanel

To evaluate the efficacy and safety of perampanel in patients with drug-resistant partial seizures after the conversion from double-blind placebo in three phase III studies to open-label perampanel, and to assess the impact of perampanel titration rates through a comparison of weekly vs biweekly dose increases. Patients who completed the three multinational, double-blind, placebo-controlled, phase III core studies (studies 304, 305, or 306) were eligible to enroll in the extension study (study 307). Patients completing the double-blind treatment (6-week titration, 13-week maintenance) with placebo (DB-PBO) or perampanel (DB-PER) began the extension study with a 16-week blinded conversion period, during which DB-PBO patients were switched to perampanel. Doses were titrated in 2-mg increments (biweekly) to an individualized maximum tolerated dose of perampanel (up to 12 mg/day). Patients then entered a planned, open-label treatment period. Perampanel treatment during the extension study reduced total seizure frequency/28 days relative to the double-blind prerandomization baseline regardless of prior perampanel or placebo treatment in the core studies. In the DB-PBO patients, median percent reductions in seizure frequency at the end of the double-blind period, at the end of the conversion period, and at Weeks 40-52 in the open-label maintenance period were 18.6%, 44.3%, and 55.0%, respectively. Seizure control was also improved in the DB-PER patients during the extension period compared to the end of the double-blind period. Responder rates were similar between the 2 patient groups at the end of the conversion period. Perampanel was well tolerated, with the most common treatment-emergent adverse events being dizziness, somnolence, weight increase, irritability, fatigue, and headache. For those patients randomized to the 12 mg group (DB-PER 12 mg), 78.4% reached the daily dose of 10 or 12 mg by the end of the 6-week titration period of the double-blind phase. By the end of the 16-week conversion period of the extension study, 64.0% of DB-PBO patients reached the daily dose of 10 or 12 mg. Seizure frequency reduction was greater after the first 13-week maintenance period of the extension study in the DB-PBO group compared to patients assigned to DB-PER 12mg during the 13-week maintenance period of the double-blind study. Patients who received placebo in the phase III core DB studies and transitioned to perampanel in the open-label extension study (DB-PBO) achieved seizure control at the end of the conversion period similar to that of patients who had been previously exposed to perampanel (DB-PER) as well as comparable safety outcomes. Patients who received perampanel during the core studies and continued with treatment during the extension study (DB-PER) also showed sustained improvements in seizure control with long-term exposure to perampanel.

Early and effective treatment of KCNQ2 encephalopathy.

To describe the antiepileptic drug (AED) treatment of patients with early infantile epileptic encephalopathy due to KCNQ2 mutations during the neonatal phase and the first year of life. We identified 15 patients and reviewed the electroclinical, neuroimaging, and AED treatment data. Seizure onset was between 1 and 4 days of age with daily tonic asymmetric, focal and clonic seizures in nine patients and status epilepticus in the remaining six. Electroencephalography (EEG) showed multifocal epileptiform abnormalities in nine patients and a burst-suppression pattern in six. All patients were trialed with adequate daily doses of several AEDs before they reached seizure freedom. Six patients (40%) achieved seizure control within 2 weeks of carbamazepine (CBZ) administration and five (33%) were seizure-free with phenytoin (PHT). The last four patients (27%) were successfully treated with topiramate (TPM) (two patients), levetiracetam (LEV) (one), and a combination of LEV with TPM (one). Most patients reached seizure freedom within the first year of life and remained seizure-free thereafter. Twelve patients had moderate-to-severe developmental delay at follow-up. However, the two patients whose seizures ceased within a few days of onset showed only mild cognitive impairment. Our findings suggest that drugs acting on sodium channels including CBZ and PHT should be considered as first-line treatment in patients with KCNQ2 encephalopathy. Voltage-gated sodium and potassium channels co-localize at the neuronal membrane. Therefore, the efficacy of drugs acting as sodium-channel blockers could be linked to their modulating effect on both channels. The type of KCNQ2 mutation might influence AED response as well as developmental outcome. Early recognition of KCNQ2 encephalopathy followed by the most appropriate and effective treatment may be important for reducing the neurodevelopmental impairment associated with this disorder.

Fish oil intake and seizure control in children with medically resistant epilepsy

Background:There is considerable evidence which suggests that Omega 3 polyunsaturated fatty acids may have a potential use in the treatment of epilepsy.Aim:The study was to investigate the effect of Omega 3 polyunsaturated fatty acids (as fish oil supplementation) in reducing the frequency and severity of epileptic seizures in children with medically resistant epilepsy.Materials and Methods:In the case-control study, a total of 70 children with medically resistant epilepsy underwent assessment of the frequency and severity of the epileptic attacks at baseline, after one month, two months and three months from the beginning of the study; 35 children received fish oil and the other 35 children received placebo.Results:The number of children who received fish oil, having 0 epileptic attacks increased from 0%, before starting the study, up to 57.1% at the end of the third month, while the improvement was minimal in the placebo group, with a significant difference in the improvement between the intervention and the control groups. There was no statistically significant difference in improvement in the severity of the seizures either between cases and control or between the beginning and the end of the study.Conclusion:Omega 3 polyunsaturated fatty acids elevated the seizure threshold in epileptic patients and may help in achieving seizure control.

Sturge-Weber Syndrome Is Associated with Cortical Dysplasia ILAE Type IIIc and Excessive Hypertrophic Pyramidal Neurons in Brain Resections for Intractable Epilepsy.

Sturge-Weber syndrome (SWS) is a rare syndrome characterized by capillary-venous malformations involving skin and brain. Many patients with SWS also suffer from drug-resistant epilepsy. We retrospectively studied a series of six SWS patients with epilepsy and extensive neurosurgical resections. At time of surgery, the patients' age ranged from 11 to 35 years (with a mean of 20.2 years). All surgical specimens were well preserved, which allowed a systematic microscopical inspection utilizing the 2011 ILAE classification for focal cortical dysplasia (FCD). Neuropathology revealed dysmorphic-like neurons with hypertrophic cell bodies reminiscent to those described for FCD type IIa in all cases. However, gross architectural abnormalities of neocortical layering typical for FCD type IIa were missing, and we propose to classify this pattern as FCD ILAE type IIIc. In addition, our patients with earliest seizure onset also showed polymicrogyria (PMG; n = 4). The ictal onset zones were identified in all patients by subdural electrodes, and these areas always showed histopathological evidence for FCD type IIIc. Four out of five patients had favorable seizure control after surgery with a mean follow-up period of 1.7 years. We concluded from our study that FCD type IIIc and PMG are frequently associated findings in SWS. FCD type IIIc may play a major epileptogenic role in SWS and complete resection of the associated FCD should be considered a prognostic key factor to achieve seizure control.

PO-0346 Review Of Life Threatening Laryngospasm, As An Isolated Symptom Of Epilepsy

Background Severe laryngospasm, as a presenting symptom of epilepsy in children, is very uncommon and often misdiagnosed. To increase awareness, we present a literature review. The incentive was a 22 month old girl who presented with life threatening laryngospasm. The choking episodes progressed rapidly to frequent unprovoked episodes day and night; associated with severe oxygen desaturation, whist being fully aware and requiring paediatric intensive care interventions. Initially, investigations did not confirm a diagnosis of epilepsy. Repeat video EEG finally demonstrated cortical seizures, with focality over the right posterior temporal region. To achieve seizure control, high doses of carbamazepine and levetiracetam were necessary. Interestingly, the patient shares neurological features with family members, suggesting a genetic link. Methods and results A literature review shows that the extent of epileptic laryngospasm in this case report has not previously been described amongst only 9 related case reports. Reviews concerning choking episodes during sleep debate a diagnostic challenge that stems from the frequent absence of recorded epileptiform activity, often causing a delay in adequate seizure treatment. Two recent reports on severe neonatal episodic laryngospasm describe a new phenotype of seizure disorder related to sodium channelopathy. In these patients, high dose carbamazepine was necessary to achieve seizure control. Conclusions Despite being a rare phenomenon, severe laryngospasm in children should be suspicious as a symptom of epilepsy, even without EEG correlation. Treatment should no be postponed, while excluding other aetiology. Carbamazepine may be effective, however high doses may be necessary to achieve seizure control. Clinical and Video EEG Available

Seizure outcomes following radiosurgery for cerebral arteriovenous malformations.

Seizures are a common presentation of cerebral arteriovenous malformations (AVMs). The authors evaluated the efficacy of stereotactic radiosurgery (SRS) for the management of seizures associated with AVMs and identified factors influencing seizure outcomes following SRS for AVMs. A systematic literature review was performed using PubMed. Studies selected for review were published in English, included at least 5 patients with both cerebral AVMs and presenting seizures treated with SRS, and provided post-SRS outcome data regarding obliteration of AVMs and/or seizures. Demographic, radiosurgical, radiological, and seizure outcome data were extracted and analyzed. All seizure outcomes were categorized as follows: 1) seizure free, 2) seizure improvement, 3) seizure unchanged, and 4) seizure worsened. Systematic statistical analysis was conducted to assess the effect of post-SRS AVM obliteration on seizure outcome. Nineteen case series with a total of 3971 AVM patients were included for analysis. Of these, 28% of patients presented with seizures, and data for 997 patients with available seizure outcome data who met the inclusion criteria were evaluated. Of these, 437 (43.8%) patients achieved seizure-free status after SRS, and 530 (68.7%) of 771 patients with available data achieved seizure control (seizure freedom or seizure improvement) following SRS. Factors associated with improved seizure outcomes following SRS for AVMs were analyzed in 9 studies. Seizure-free status was achieved in 82% and 41.0% of patients with complete and incomplete AVM obliteration, respectively. Complete AVM obliteration offered superior seizure-free rates compared with incomplete AVM obliteration (OR 6.13; 95% CI 2.16-17.44; p = 0.0007). Stereotactic radiosurgery offers favorable seizure outcomes for AVM patients presenting with seizures. Improved seizure control is significantly more likely with complete AVM obliteration.

ABSTRACT 329

Background and aims: Status Epilepticus (SE) continues to be one of the most common pediatric acute care emergencies. Conventional SE protocols advocate Phenobarbitone as a second line antiepileptic drug (AED) if the child continues to seize even after Benzodiazepine (BZD) and Fosphenytoin (FPE) loading. Aims: We aimed to investigate the efficacy and safety of Levetiracetam as stage two AED in pediatric SE in place of phenobarbitone. Methods: Study design: Prospective observational study All consecutive children admitted to pediatric emergency during the study period (Jan 2012 to Nov 2013) received second stage AED Levetiracetam to control SE were included in the study to describe the safety and efficacy of Levetiracetam. Results: Of 111 children admitted with convulsive SE during the study period, 33 (36.7%) received Levetiracetam as stage two AED to achieve seizure control. Intravenous Levetiracetam at 30 mg/kg over 15 minutes followed by 10 mg/kg/dose as maintenance at 8 hourly interval was administered in all those enrolled. The mean age of presentation was 45.6 months [45.6(20.5–70.7)]. Among those received Levetiracetam, 22 children [67%; 22/33] had first episode seizure presenting as SE and 11 children [33%; 11/33] have had prior history of seizure. Levetiracetam had comparable efficacy (84%) and time to abort SE (16 min) to phenobarbitone as second stage AED without any side effects. Conclusions: This study concludes that Levetiracetam has comparable efficacy to be used as a second line AED in managing convulsive SE in infants and children with better side effect profile.

Low threshold T‐type calcium channels as targets for novel epilepsy treatments

Low voltage-activated T-type calcium channels were originally cloned in the 1990s and much research has since focused on identifying the physiological roles of these channels in health and disease states. T-type calcium channels are expressed widely throughout the brain and peripheral tissues, and thus have been proposed as therapeutic targets for a variety of diseases such as epilepsy, insomnia, pain, cancer and hypertension. This review discusses the literature concerning the role of T-type calcium channels in physiological and pathological processes related to epilepsy. T-type calcium channels have been implicated in pathology of both the genetic and acquired epilepsies and several anti-epileptic drugs (AEDs) in clinical use are known to suppress seizures via inhibition of T-type calcium channels. Despite the fact that more than 15 new AEDs have become clinically available over the past 20 years at least 30% of epilepsy patients still fail to achieve seizure control, and many patients experience unwanted side effects. Furthermore there are no treatments that prevent the development of epilepsy or mitigate the epileptic state once established. Therefore there is an urgent need for the development of new AEDs that are effective in patients with drug resistant epilepsy, are anti-epileptogenic and are better tolerated. We also review the mechanisms of action of the current AEDs with known effects on T-type calcium channels and discuss novel compounds that are being investigated as new treatments for epilepsy.

Adherence to antiepileptic drugs among children attending a tertiary health unit in a low resource setting.

IntroductionEpilepsy is one of the neglected and highly stigmatised diseases, yet it is very common affecting about 70 million people worldwide. In Uganda, the estimated prevalence of epilepsy is 13% with about 156 new cases per 100,000 people per year. Adherence to antiepileptic drugs is crucial in achieving seizure control yet in Uganda; there is lack of information on adherence to antiepileptic drugs and the factors that affect this among children. This study was therefore designed to determine the level of adherence to antiepileptic drugs and the factors that are associated with non adherence.MethodsIn a cross sectional study, 122 children who met the inclusion criteria were enrolled and interviewed using a pretested questionnaire. Assessment of adherence to antiepileptic drugs was done by self report and assay of serum drug levels of the antiepileptic drugs. Focus group discussions were held to further evaluate the factors that affect adherence.ResultsAge range was 6 months - 16 years, male to female ratio 1.3:1 and majority had generalised seizures 76 (62.3%). Adherence to antiepileptic drugs by self report was 79.5% and 22.1% by drug levels. Majority of the children in both adherent and non adherent groups by self report had inadequate drug doses (95/122). Children were found to be more non-adherent if the caregiver had an occupation (p-value 0.030, 95%CI 1.18-28.78)ConclusionMajority of children had good adherence levels when estimated by self report. The caregiver having an occupation was found to increase the likelihood of non adherence in a child.

U centru epilepsije - povodom proslave 90-godišnjice Neurološke klinike u Beogradu

The most important and simplest form of epilepsy treatment is the application of antiepileptic drugs. Its goal is to prevent the recurrence of epileptic attacks without provoking significant side effects. Unfortunately, in about 20-30% of patients antiepileptic drugs does not achieve seizure control. In a number of patients with pharmacoresistant focal epilepsy resective brain surgery is the optimal treatment method. Our experience as well as of the other epilepsy centers indicates that appropriate methods of preoperative evaluation and advanced techniques in epilepsy surgery are effective and safe methods of treatment resistant epilepsy, particularly temporal lobe epilepsy. Surgical treatment of pharmacoresistant focal epilepsy leads to full control of seizures in about 2/3 of the operated patients. In order to achieve the complete surgical success, it is necessary to remove or disconnect that area or part of the brain, which is responsible for the initiation of epileptic seizures. That part of the brain (i.e. cerebral cortex) is called the epileptogenic zone and should be removed with the maximum refrain from those parts of the brain responsible for an important function (i.e."eloquent" cortex). Different modalities of diagnostic tests that are now used as part of presurgical evaluation (video-EEG telemetry, magnetic resonance imaging, neuropsychological testing, functional neuroradiology), allow the precise localization of the epileptogenic zone in majority of patients.

Seizure control for intracranial arteriovenous malformations is directly related to treatment modality: a meta-analysis

ObjectSeizures are a common presenting sign of intracranial arteriovenous malformations (AVMs). The object of this meta-analysis was to determine if the modality selected to treat AVMs affects the rate of...

Patient satisfaction with temporal lobectomy/selective amygdalohippocampectomy for temporal lobe epilepsy and its relationship with Engel classification and the side of lobectomy

PurposeThe aim of this study was to investigate not only the effectiveness of epilepsy surgery in improving seizure control but also patient satisfaction with the result of the procedure in a sample of patients operated on at a specialized epilepsy unit. MethodsPatients with temporal lobe epilepsy who had undergone epilepsy surgery (temporal lobectomy/amygdalohippocampectomy) were interviewed in a standardized telephone survey about their satisfaction with the results of the surgery. The morbidity of the surgery was also analyzed retrospectively. The initial study population consisted of 6 amygdalohippocampectomy and 102 temporal lobectomy patients and was reduced to a final sample consisting of 4 amygdalohippocampectomy and 67 lobectomy patients, as the other patients were not available for interview. Surgical results were based on the Engel classification, and satisfaction with the surgery was assessed by asking patients to rate their result and state whether they would make the same decision (to be operated on) again. ResultsA significant number of patients classified as Engel I or II, who considered the surgical outcome good or excellent, said they would have the surgery again (p<0.001). Left temporal lobectomy patients whose results fell in the Engel III/IV bracket were less satisfied (p=0.001) than right temporal lobectomy patients with the same Engel classifications (0.048). Left temporal lobectomy patients who were classified as Engel class III and IV were less likely to have the surgery again if they had the choice (p=0.016). DiscussionPatient satisfaction with the results of epilepsy surgery may depend not only on achieving seizure control but also on the temporal lobe resected. Since worse results were associated with lower satisfaction rates only for left temporal resection patients, it is possible that the cognitive consequences of this procedure compound the worse surgical result, leading to decreased satisfaction.

The cortical excitability profile of temporal lobe epilepsy

Transcranial magnetic stimulation (TMS) was used to characterize measurable changes of cortical excitability in patients who were undergoing medical and surgical management of temporal lobe epilepsy (TLE) to investigate whether these alterations depended on timing of achieving seizure control throughout the course of illness and method of management. Eighty-five patients with TLE divided into (1) drug naive-new onset, (2) early medically refractor, and (3) late medically refractory, (4) early seizure-free on antiepileptic drugs, and (5) late seizure-free on antiepileptic drugs, (6) postoperative refractory, and (7) postoperative seizure-free groups were studied. Motor threshold (MT) and paired-pulse TMS at short (2, 5, 10, and 15 msec) and long (100-300 msec) interstimulus intervals (ISIs) were measured. Results were compared to those of 20 controls. A significant interhemispheric difference was observed early at onset prior to starting medication, with higher cortical excitability in the hemisphere ipsilateral to the seizure focus, whereas the unaffected hemisphere was normal. After that, cortical excitability was higher in both hemispheres in the refractory groups (medical and postoperative) compared to the seizure-free and drug-naive groups (p < 0.05). This effect was most prominent at the long ISIs. Changes in cortical excitability seen in patients with TLE are influenced by the course of the disease. The alterations that occur due to epilepsy are closely related to course of illness and degree/timing of seizure control. Successful management leads to resolution of this cortical hyperexcitability in a similar fashion regardless of method: medication (intact generator, but modulated by drugs) or surgery (generator removed).

Cognitive outcomes of different surgical approaches in temporal lobe epilepsy

Epilepsy surgery is a successful treatment option for pharmacoresistant focal symptomatic epilepsies. However, cognitive impairment is very common in epilepsy patients and may be negatively or positively affected by surgery. Amidst the long-standing discussion of whether a particular surgical approach for temporal lobe epilepsy patients may be superior with regards to seizure control, a recent meta-analysis indicated that this is the case for more extended resections. Larger temporal lobe resections, however, raise concerns that more unaffected and functional tissues may be involved, thus causing worse cognitive outcome. This review is based on published reports collected over a long period, with changing diagnostics and surgical methods, and focuses mainly on the experiences of one epilepsy centre. The review highlights the effects of standard versus selective surgery, the different surgical approaches in selective surgery, determinants other than surgery which may affect cognitive outcome, and the methodologically-important question of outcome assessment and how neuropsychological test selection may bias the result. Overall, from a neuropsychological point of view, individual and selective surgery is preferred in which the aim is to achieve seizure control with minimal effect on the functional integrity of tissues or fibre tracts. Cognition is important for the functions of everyday life and this should be kept in mind, irrespective of which kind of surgery is preferred.

Image registration of ex-vivo MRI to sparsely sectioned histology of hippocampal and neocortical temporal lobe specimens

Intractable or drug-resistant epilepsy occurs in up to 30% of epilepsy patients, with many of these patients undergoing surgical excision of the affected brain region to achieve seizure control. Recent magnetic resonance imaging (MRI) sequences and analysis techniques have the potential to detect abnormalities not identified with diagnostic MRI protocols. Prospective studies involving pre-operative imaging and collection of surgically-resected tissue provide a unique opportunity for verification and tuning of these image analysis techniques, since direct comparison can be made against histopathology, and can lead to better prediction of surgical outcomes and potentially less invasive procedures. To carry out MRI and histology comparison, spatial correspondence between the MR images and the histology images must be found. Towards this goal, a novel pipeline is presented here for bringing ex-vivo MRI of surgically-resected temporal lobe specimens and digital histology into spatial correspondence. The sparsely-sectioned histology images represent a challenge for 3D reconstruction which we address with a combined 3D and 2D registration algorithm that alternates between slice-based and volume-based registration with the ex-vivo MRI. We evaluated our registration method on specimens resected from patients undergoing anterior temporal lobectomy (N=7) and found our method to have a mean target registration error of 0.76±0.66 and 0.98±0.60mm for hippocampal and neocortical specimens respectively. This work allows for the spatially-local comparison of histology with post-operative MRI and paves the way for eventual correlation with pre-operative MRI image analysis techniques.

Surgical Treatment of Epilepsy

This article outlines indications for neurosurgical treatment of epilepsy, describes the presurgical workup, summarizes surgical approaches, and details expected risks and benefits. There is class I evidence for the efficacy of temporal lobectomy in treating intractable seizures, and accumulating documentation that successful surgical treatment reverses much of the disability, morbidity, and excess mortality of chronic epilepsy. Chronic, uncontrolled focal epilepsy causes progressive disability and increased mortality, but these can be reversed with seizure control. Vigorous efforts to stop seizures are warranted. If two well-chosen and tolerated medication trials do not achieve seizure control, an early workup for epilepsy surgery should be arranged. If this workup definitively identifies the brain region from which the seizures arise, and this region can be removed with a low risk of disabling neurologic deficits, neurosurgery will have a much better chance of stopping seizures than further medication trials.

What predicts enduring intractability in children who appear medically intractable in the first 2 years after diagnosis?

In a population-based retrospective cohort of children with newly diagnosed epilepsy, to determine (1) what proportion meet criteria for early medical intractability, and (2) predictors of enduring intractability. Children with newly diagnosed epilepsy between 1980 and 2009 while resident in Olmsted County, MN, and followed >36 months, were stratified into groups based on both early medical intractability ("apparent" medical intractability in the first 2 years) and enduring intractability (persisting intractability at final follow-up or having undergone surgery for intractable epilepsy), and variables predicting these outcomes were evaluated. Three hundred eighty-one children were included, representing 81% of our cohort with newly diagnosed epilepsy. Seventy five (19.7%) had early medical intractability, and predictors of this outcome on multivariable analysis were neuroimaging abnormality (risk ratio, 2.70; p = 0.0004), abnormal neurologic examination at diagnosis (risk ratio, 1.87; p = 0.015), and mode of onset (association was significant for focal vs. generalized onset [risk ratio, 0.25; p < 0.0001] but not unknown vs. generalized onset [p = 0.065]). After a median follow-up of 11.7 years, 49% remained intractable, 8% had rare seizures (≤ every 6 months), and the remainder were seizure-free. The only factor predicting enduring intractability on multivariable analysis was neuroimaging abnormality (risk ratio, 7.0; p = 0.0006). Although a significant minority of children with early medical intractability ultimately achieved seizure control without surgery, those with an abnormal imaging study did poorly. For this subgroup, early surgical intervention is strongly advised to limit comorbidities of ongoing, intractable seizures. Conversely, a cautious approach is suggested for those with normal imaging, as most will remit with time.

Outcome of newly-diagnosed epilepsy in older patients

IntroductionThe annual incidence of seizure disorders rises sharply after the age of 60. Treatment is complicated by the normal physiological changes of aging, comorbid diseases, and polypharmacy. Despite this, approximately 80% of the patients become seizure-free. ObjectivesThe objectives of this study were to (1) analyze the outcome of a cohort of patients with newly-diagnosed epilepsy over the age of 65, (2) describe epilepsy etiology and seizure type, and (3) classify the outcome according to the latest ILAE classification proposal for drug-resistant epilepsy (2010). MethodsAll patients with newly-diagnosed epilepsy over the age of 65 who were evaluated in two different institutions were included. Seizures and epilepsy syndromes were classified according to the International League Against Epilepsy proposal (2010). Epilepsy outcomes were also analyzed according to the proposal of the ILAE Commission on Therapeutic Strategies (2010). ResultsOne hundred and twenty-two patients were included with a median follow-up time of 15months. Median age of diagnosis was 78years. Seventy-seven patients (55%) had epilepsy of unknown cause, and 55 (45%) had structural–metabolic epilepsy. The proportions of seizure-free patients at 6, 12, 18, and 24months were 90%, 77%, 74%, and 67%, respectively. Thirty percent of patients experienced adverse effects (AEs). We found a statistically significant trend toward a higher frequency of AEs as the number of concomitant medications rose and in younger patients. According to the 2010 ILAE classification proposal for drug-resistant epilepsy criteria, 55.8% of the patients were seizure-free, 12.3% had treatment failure, and 32% had undetermined seizure outcome. ConclusionPatients with newly-diagnosed epilepsy after the age of 65 have very good chances of achieving seizure control with AED treatment. It seems that fulfilling the ILAE classification proposal for drug-resistant epilepsy (2010) criteria for seizure freedom was more difficult in our cohort. Older patients also seem to be more prone to suffering from AEs.

Nonrandomness, nonlinear dependence, and nonstationarity of electroencephalographic recordings from epilepsy patients

To derive tests for randomness, nonlinear-independence, and stationarity, we combine surrogates with a nonlinear prediction error, a nonlinear interdependence measure, and linear variability measures, respectively. We apply these tests to intracranial electroencephalographic recordings (EEG) from patients suffering from pharmacoresistant focal-onset epilepsy. These recordings had been performed prior to and independent from our study as part of the epilepsy diagnostics. The clinical purpose of these recordings was to delineate the brain areas to be surgically removed in each individual patient in order to achieve seizure control. This allowed us to define two distinct sets of signals: One set of signals recorded from brain areas where the first ictal EEG signal changes were detected as judged by expert visual inspection ("focal signals") and one set of signals recorded from brain areas that were not involved at seizure onset ("nonfocal signals"). We find more rejections for both the randomness and the nonlinear-independence test for focal versus nonfocal signals. In contrast more rejections of the stationarity test are found for nonfocal signals. Furthermore, while for nonfocal signals the rejection of the stationarity test increases the rejection probability of the randomness and nonlinear-independence test substantially, we find a much weaker influence for the focal signals. In consequence, the contrast between the focal and nonfocal signals obtained from the randomness and nonlinear-independence test is further enhanced when we exclude signals for which the stationarity test is rejected. To study the dependence between the randomness and nonlinear-independence test we include only focal signals for which the stationarity test is not rejected. We show that the rejection of these two tests correlates across signals. The rejection of either test is, however, neither necessary nor sufficient for the rejection of the other test. Thus, our results suggest that EEG signals from epileptogenic brain areas are less random, more nonlinear-dependent, and more stationary compared to signals recorded from nonepileptogenic brain areas. We provide the data, source code, and detailed results in the public domain.

Defining Clinico‐Neuropathological Subtypes of Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis

Hippocampal sclerosis (HS) is the most frequent cause of drug-resistant focal epilepsies (ie, mesial temporal lobe epilepsy with hippocampal sclerosis; mTLE-HS), and presents a broad spectrum of electroclinical, structural and molecular pathology patterns. Many patients become drug resistant during the course of the disease, and surgical treatment was proven helpful to achieve seizure control. Hence, up to 40% of patients suffer from early or late surgical failures. Different patterns of hippocampal cell loss, involvement of other mesial temporal structures, as well as temporal neocortex including focal cortical dysplasia, may contribute to the extent of the epileptogenic network and will be discussed. An international consensus is mandatory to clarify terminology use and to reliably distinguish mTLE-HS subtypes. High-resolution imaging with confirmed histopathologic diagnosis, as well as advanced neurophysiologic and molecular genetic measures, will be a powerful tool in the future to address these issues and help to predict each patient's probability to control their epilepsy in mTLE-HS conditions.