Achieved Seizure Freedom Research Articles

Short-term Seizure Outcomes in Childhood Epilepsy.

Seizure freedom is the optimal response to antiepileptic treatment. In previous studies, it has been shown that between 61% and 71% of children with epilepsy achieve seizure freedom, whereas 7% to 20% have drug-resistant epilepsy. The definition of drug resistance has not been consistent across studies, and there is a lack of contemporary population-based data. We used data from a large nationwide child cohort to provide such information, implementing the current standard definition of drug resistance. The study was based on the Norwegian Mother and Child Cohort Study. Potential epilepsy cases were identified through registry linkages and parental questionnaires. Medical record reviews and parental interviews were used to collect clinical information and to classify seizures, epilepsies, and etiologies. The cohort included 112 745 eligible children aged 3 to 13 years (median age 7 years) at end of follow-up. Of these, 600 were epilepsy cases with at least 1 year of follow-up since epilepsy onset (median follow-up time: 5.8 years). There were 178 (30%) who had developed drug-resistant epilepsy, 353 (59%) who had been seizure free for ≥1 year, and 69 (12%) with intermediate seizure outcomes. Having an identified cause of epilepsy (genetic, structural, metabolic, or infectious) was associated with unsatisfactory seizure outcome (48% drug resistance) and influenced the relative risk associated with other prognostic factors. Sociodemographic characteristics were not associated with short-term seizure outcomes. Drug resistance occurs in 3 out of 10 children with epilepsy, whereas 6 out of 10 become seizure free. Having an identified cause of epilepsy is associated with poor response to treatment.

Platform Session – Electroencephalography/Epilepsy: Magnetoencephalography imaging of surgically resected inter-ictal high frequency oscillation (80–200 Hz) was associated with seizure freedom

Introduction Accurate delineation of epileptogenic zone(EZ) is crucial in patients with medically refractory epilepsy (MRE) warranting surgery and at least 33% will have seizure recurrence post-surgery. Intracranial EEG studies had showed that high frequency oscillations (HFO; 80–200 Hz) can accurately localize the EZ and patients had better post-surgical seizure freedom, if brain regions generating HFOs were resected out. However, none of the noninvasive studies evaluated the clinical utility of HFOs. So, we investigated epileptic HFOs source imaging to delineate the presurgical EZ and predict the seizure freedom. Methods Fifty-two patients (M: F = 37:15; age = 23 ± 8.9 years; disease duration 11.4 ± 7.7 years) with MRE were longitudinally recruited and studied with MEG. Each interictal epileptic discharge were marked by assessing spatial topography. Subject specific semi-realistic head model and a 3D grid voxels of 10 mm resolution was constructed. Source reconstruction was performed with frequency beamformer, by attenuating the source power at a specified location, subject to unit-gain constraint. Gain matrix was determined and cross-spectral density matrix on a Fourier transformed data was calculated at 7 distinct frequency bands; 8–14 Hz, 14–30 Hz, 1–30 Hz, 30–54 Hz, 55–80 Hz, 30–80 Hz, and 80–200 Hz. From the available clinical data, EZ was defined, respective surgery was performed and surgical outcome was assessed. The congruency of source construction with the EZ and surgically resected cortex was established at four levels, for each band & strength was quantified by kappa statistic. Sensitivity, positive predictive value (PPV) and accuracy was evaluated. Source localization error (SLE) was determined on the basis of minimum euclidean distance between the margin of reconstructed sources with the volume of the resected cortex. Results With surgery, 44 (84.6%) patients had good (Engel-I) and 8 (15.4%) patients had poor (Engel-II-IV) clinical outcome at 22.1 ± 10 months follow up. Compared to other frequency bands, interictal HFO imaging accurately delineated the epileptogenic cortex in 80.3% (k = 0.44 ± 0.12) of the patients, with 80.8% sensitivity, 100% PPV, and 80.32% accuracy. The highest possible concordance rate of 78.8% (k = 0.46 ± 0.1) with the surgically resected cortical volume, was observed for the reconstructed HFO sources. HFO source reconstruction did correlate with the seizure freedom (p Conclusion To date, this is the first ever largest prospective & noninvasive (MEG) study to investigate the clinical role of the HFOs, where HFOs precisely delineated the EZ & predicted the patients who might achieve seizure freedom with surgery, emerging as a key noninvasive epilepsy biomarker.

Predictive factors of higher drug load for seizure freedom in idiopathic generalized epilepsy: Comparison between juvenile myoclonic epilepsy and other types

PurposePredictive factors of higher drug load for seizure freedom were investigated in idiopathic generalized epilepsy (IGE), focusing on the difference between juvenile myoclonic epilepsy (JME) and other types of IGE (non-JME IGE). MethodsTwelve patients with JME and 12 patients with non-JME IGE, who achieved seizure freedom for 1 year or longer with appropriate antiepileptic drugs (AEDs) after video electroencephalography monitoring, were reviewed retrospectively. The sum of prescribed daily dose/defined daily dose ratio of all prescribed AEDs at the final visit was defined as total AED load. Patients requiring total AED load >1 were classified into the higher AED load group. Clinical background and the presence of interictal focal epileptiform abnormalities (FEAs) were compared between the higher and lower AED load groups. ResultsHigher AED load group of patients with JME had interictal FEAs and family history of epilepsy more frequently than the lower AED load group (p = 0.03 and p = 0.03). Similar comparison of patients with non-JME IGE showed no significant differences. ConclusionsThe presence of interictal FEAs and a family history of epilepsy are significantly associated variables for higher AED load for seizure freedom in patients with JME, but not in patients with non-JME IGE.

Surgical treatment for refractory epilepsy

The goal of any epilepsy surgery is to improve patient's quality of life by achieving seizure freedom or by reducing the frequency of severely debilitating seizures. To achieve this goal, non-invasive and invasive diagnostic methods must precisely delineate the epileptogenic zone (EZ), which is defined as the area that needs to be resected to obtain seizure freedom. At the same time, the correct identification of eloquent brain areas is inevitable to avoid new neurological deficits from surgery. In recent years, the technical advances in diagnostics have enabled us to achieve these goals in an increasing number of cases. As a consequence, and with new surgical treatment options available, the number of patients who might benefit from epilepsy surgery is constantly increasing. Especially in pediatric epilepsy, early surgical intervention is becoming frequently advocated as it has been shown to improve cognitive and behavioral outcome. Specialized epilepsy centers and multidisciplinary teams are required to provide adequate care and treatment. The goal of this review is to describe important diseases that are accessible to epilepsy surgery and to give an overview of current diagnostic methods. The focus lies on established as well as novel techniques in epilepsy surgery. The presurgical work-up and patient selection is outlined.

Advanced dynamic statistical parametric mapping with MEG in localizing epileptogenicity of the bottom of sulcus dysplasia

ObjectiveTo investigate whether advanced dynamic statistical parametric mapping (AdSPM) using magnetoencephalography (MEG) can better localize focal cortical dysplasia at bottom of sulcus (FCDB). MethodsWe analyzed 15 children with diagnosis of FCDB in surgical specimen and 3 T MRI by using MEG. Using AdSPM, we analyzed a ±50 ms epoch relative to each single moving dipole (SMD) and applied summation technique to estimate the source activity. The most active area in AdSPM was defined as the location of AdSPM spike source. We compared spatial congruence between MRI-visible FCDB and (1) dipole cluster in SMD method; and (2) AdSPM spike source. ResultsAdSPM localized FCDB in 12 (80%) of 15 children whereas dipole cluster localized six (40%). AdSPM spike source was concordant within seizure onset zone in nine (82%) of 11 children with intracranial video EEG. Eleven children with resective surgery achieved seizure freedom with follow-up period of 1.9 ± 1.5 years. Ten (91%) of them had an AdSPM spike source in the resection area. ConclusionAdSPM can noninvasively and neurophysiologically localize epileptogenic FCDB, whether it overlaps with the dipole cluster or not. SignificanceThis is the first study to localize epileptogenic FCDB using MEG.

Betweenness centrality of intracranial electroencephalography networks and surgical epilepsy outcome

ObjectiveWe sought to determine whether the presence or surgical removal of certain nodes in a connectivity network constructed from intracranial electroencephalography recordings determines postoperative seizure freedom in surgical epilepsy patients. MethodsWe analyzed connectivity networks constructed from peri-ictal intracranial electroencephalography of surgical epilepsy patients before a tailored resection. Thirty-six patients and 123 seizures were analyzed. Their Engel class postsurgical seizure outcome was determined at least one year after surgery. Betweenness centrality, a measure of a node’s importance as a hub in the network, was used to compare nodes. ResultsThe presence of larger quantities of high-betweenness nodes in interictal and postictal networks was associated with failure to achieve seizure freedom from the surgery (p < 0.001), as was resection of high-betweenness nodes in three successive frequency groups in mid-seizure networks (p < 0.001). ConclusionsBetweenness centrality is a biomarker for postsurgical seizure outcomes. The presence of high-betweenness nodes in interictal and postictal networks can predict patient outcome independent of resection. Additionally, since their resection is associated with worse seizure outcomes, the mid-seizure network high-betweenness centrality nodes may represent hubs in self-regulatory networks that inhibit or help terminate seizures. SignificanceThis is the first study to identify network nodes that are possibly protective in epilepsy.

Automated trajectory planning for laser interstitial thermal therapy in mesial temporal lobe epilepsy

SummaryObjectiveSurgical resection of the mesial temporal structures brings seizure remission in 65% of individuals with drug‐resistant mesial temporal lobe epilepsy (MTLE). Laser interstitial thermal therapy (LiTT) is a novel therapy that may provide a minimally invasive means of ablating the mesial temporal structures with similar outcomes, while minimizing damage to the neocortex. Systematic trajectory planning helps ensure safety and optimal seizure freedom through adequate ablation of the amygdalohippocampal complex (AHC). Previous studies have highlighted the relationship between the residual unablated mesial hippocampal head and failure to achieve seizure freedom. We aim to implement computer‐assisted planning (CAP) to improve the ablation volume and safety of LiTT trajectories.MethodsTwenty‐five patients who had previously undergone LiTT for MTLE were studied retrospectively. The EpiNav platform was used to automatically generate an optimal ablation trajectory, which was compared with the previous manually planned and implemented trajectory. Expected ablation volumes and safety profiles of each trajectory were modeled. The implemented laser trajectory and achieved ablation of mesial temporal lobe structures were quantified and correlated with seizure outcome.Results CAP automatically generated feasible trajectories with reduced overall risk metrics (P < .001) and intracerebral length (P = .007). There was a significant correlation between the actual and retrospective CAP‐anticipated ablation volumes, supporting a 15 mm diameter ablation zone model (P < .001). CAP trajectories would have provided significantly greater ablation of the amygdala (P = .0004) and AHC (P = .008), resulting in less residual unablated mesial hippocampal head (P = .001), and reduced ablation of the parahippocampal gyrus (P = .02).SignificanceCompared to manually planned trajectories CAP provides a better safety profile, with potentially improved seizure‐free outcome and reduced neuropsychological deficits, following LiTT for MTLE.

The management of epilepsy in children and adults.

The International League Against Epilepsy has recently published a new classification of epileptic seizures and epilepsies to reflect the major scientific advances in our understanding of the epilepsies since the last formal classification 28 years ago. The classification emphasises the importance of aetiology, which allows the optimisation of management. Antiepileptic drugs (AEDs) are the main approach to epilepsy treatment and achieve seizure freedom in about two-thirds of patients. More than 15 second generation AEDs have been introduced since the 1990s, expanding opportunities to tailor treatment for each patient. However, they have not substantially altered the overall seizure-free outcomes. Epilepsy surgery is the most effective treatment for drug-resistant focal epilepsy and should be considered as soon as appropriate trials of two AEDs have failed. The success of epilepsy surgery is influenced by different factors, including epilepsy syndrome, presence and type of epileptogenic lesion, and duration of post-operative follow-up. For patients who are not eligible for epilepsy surgery or for whom surgery has failed, trials of alternative AEDs or other non-pharmacological therapies, such as the ketogenic diet and neurostimulation, may improve seizure control. Ongoing research into novel antiepileptic agents, improved techniques to optimise epilepsy surgery, and other non-pharmacological therapies fuel hope to reduce the proportion of individuals with uncontrolled seizures. With the plethora of gene discoveries in the epilepsies, "precision therapies" specifically targeting the molecular underpinnings are beginning to emerge and hold great promise for future therapeutic approaches.

The ketogenic diet is effective for refractory epilepsy associated with acquired structural epileptic encephalopathy.

Ketogenic diet therapies have proven efficacy for refractory epilepsy. There are many reports of their use in the genetic developmental and epileptic encephalopathies; however, little attention has been paid as to whether the diet is also effective in individuals with an acquired structural aetiology. We observed remarkable efficacy of the diet in two patients with hypoxic-ischaemic encephalopathy. We then analysed our cases with refractory structural epilepsies of acquired origin to characterize their response to the ketogenic diet. The classical ketogenic diet was implemented with dietary ratios of 3:1 to 4.4:1. Seizure frequency at 1month, 3months, 6months, 1year, and 2years was ascertained. A responder was defined as greater than 50% seizure reduction compared to baseline. Seven of the nine patients were responders at 3months. Somewhat surprisingly we found that the ketogenic diet was effective in patients with a developmental and epileptic encephalopathy due to an acquired structural aetiology. This cohort may not be routinely considered for the ketogenic diet because of their structural and acquired, rather than genetic, basis. The ketogenic diet should be considered early in the management of patients with acquired structural encephalopathies as it can improve seizure control with the potential to improve developmental outcome. The ketogenic diet was effective in children with epilepsy associated with an acquired structural aetiology.

Ketogenic Diet Therapy in Infants: Efficacy and Tolerability

PurposeThis study evaluated tolerability and efficacy of the ketogenic diet in infants less than 12 months of age. MethodsInfants less than 12 months of age, commencing the ketogenic diet between September 2007 and July 2016 were identified. Records were reviewed for epilepsy details, diet initiation details, efficacy and tolerability. ResultsTwenty-seven infants commenced the ketogenic diet (56% male, median age seven months). Median age at seizure onset was 1.9 months and 92% had daily seizures. An epilepsy syndrome was noted in 19 (West-11, epilepsy in infancy with migrating focal seizures-5, early myoclonic encephalopathy-1, Ohtahara-1, Dravet-1). Infants were on a median of two and had failed a median of one medications for lack of efficacy. All initiated a traditional ketogenic diet at full calories without fasting, and all but one started the diet in hospital.Significant hypoglycemia during initiation was seen in two - both had emesis +/- decreased oral intake. Eighty-eight percent developed urinary ketosis by 48 hours and all were successfully discharged on the diet (median ratio 3:1).Of those continuing dietary therapy, responder rates at one, six and 12 months were 68%, 82% and 91%, with 20%, 29% and 27% achieving seizure freedom. By 12 months, two stopped the diet for serious adverse effects, five discontinued for lack of efficacy, six were lost to follow-up and two died of unrelated causes. ConclusionsThe ketogenic diet is an effective and well-tolerated treatment for infants with intractable epilepsy. In-hospital initiation is strongly recommended due to risk of hypoglycemia with emesis or reduced intake.

Electroclinical findings and long-term outcomes in epileptic patients with inv dup (15).

To define the electroclinical phenotype and long-term outcomes in a cohort of patients with inv dup (15) syndrome. The electroclinical data of 45 patients (25 males) affected by inv dup (15) and seizures were retrospectively analysed, and long-term follow-up of epilepsy was evaluated. Epilepsy onset was marked by generalized seizures in 53% of patients, epileptic spasms in 51%, focal seizures in 26%, atypical absences in 11% and epileptic falls in 9%. The epileptic syndromes defined were: generalized epilepsy (26.7%), focal epilepsy (22.3%), epileptic encephalopathy with epileptic spasms as the only seizure type (17.7%) and Lennox-Gastaut syndrome (33.3%). Drug-resistant epilepsy was detected in 55.5% of patients. There was a significant higher prevalence of seizure-free patients in those with seizure onset after the age of 5years and with focal epilepsy, with respect to those with earlier epilepsy onset because most of these later developed an epileptic encephalopathy (69.2% vs 34.4%; P=.03), usually Lennox-Gastaut Syndrome in type. In fact, among patients with early-onset epilepsy, those presenting with epileptic spasms as the only seizure type associated with classical hypsarrhythmia achieved seizure freedom (P<.001) compared to patients with spasms and other seizure types associated with modified hypsarrhythmia. Epilepsy in inv dup (15) leads to a more severe burden of disease. Frequently, these patients show drug resistance, in particular when epilepsy onset is before the age of five and features epileptic encephalopathy.

Losigamone add-on therapy for focal epilepsy.

Epilepsy is a common neurologic disorder, affecting approximately 50 million people worldwide; nearly a third of these people have epilepsy that is not well controlled by a single antiepileptic drug (AED) and they usually require treatment with a combination of two or more AEDs. In recent years, many newer AEDs have been investigated as add-on therapy for focal epilepsy; losigamone is one of these drugs and is the focus of this systematic review. This is an update of a Cochrane review first published in 2012 (Cochrane Database of Systematic Reviews 2012, Issue 6) and updated in 2015. To investigate the efficacy and safety of losigamone when used as an add-on therapy for focal epilepsy. For the latest update on 9 February 2017, we searched the Cochrane Epilepsy Specialized Register, CENTRAL and MEDLINE . We searched trials registers and contacted themanufacturer of losigamone and authors of included studies for additional information. We did not impose any language restrictions. Randomized controlled, add-on trials comparing losigamone with placebo for focal epilepsy. Two review authors independently assessed trial quality and extracted data. The primary outcomes were 50% or greater reduction in seizure frequency and seizure freedom; the secondary outcomes were treatment withdrawal and adverse events. Results are presented as risk ratios (RRs) with 95% confidence intervals (CIs) or 99% CIs (for the individual listed adverse events to make an allowance for multiple testing). Two trials involving a total of 467 participants, aged over 18 years, were eligible for inclusion. Both trials assessed losigamone 1200 mg/day or 1500 mg/day as an add-on therapy for focal epilepsy. We assessed one trial as being of good methodological quality while the other was of uncertain quality. For the efficacy outcomes, results did show that participants taking losigamone were significantly more likely to achieve a 50% or greater reduction in seizure frequency (RR 1.76, 95% CI 1.14 to 2.72), but associated with a significant increase of treatment withdrawal when compared with those taking placebo (RR 2.16, 95% CI 1.28 to 3.67). For the safety outcomes, results indicated that the proportion of participants who experienced adverse events in the losigamone group was higher than in the placebo group (RR 1.34, 95% CI 1.00 to 1.80), dizziness was the only adverse event significantly reported in relation to losigamone (RR 3.82, 99% CI 1.69 to 8.64). The proportion of participants achieving seizure freedom was not reported in either trial report. A subgroup analysis according to different doses of losigamone showed that a higher dose of losigamone (1500 mg/day) was associated with a greater reduction in seizure frequency than lower doses, but was also associated with more dropouts due to adverse events. The results of this review showed that losigamone did reduce seizure frequency but was associated with more treatment withdrawals when used as an add-on therapy for people with focal epilepsy. However, the included trials were of short-term duration and uncertain quality. Future well-designed randomized, double-blind, placebo-controlled trials with a longer-term duration are needed. No new studies have been found since the last version of this review. We judged the overall quality of the evidence for the outcomes assessed as moderate.

Strong coupling between slow oscillations and wide fast ripples in children with epileptic spasms: Investigation of modulation index and occurrence rate.

Epileptic spasms (ES) often become drug-resistant. To reveal the electrophysiological difference between children with ES (ES+) and without ES (ES-), we compared the occurrence rate (OR) of high-frequency oscillations (HFOs) and the modulation index (MI) of coupling between slow and fast oscillations. In ES+, we hypothesized that (1) pathological HFOs are more widely distributed and (2) slow oscillations show stronger coupling with pathological HFOs than in ES-. We retrospectively reviewed 24 children with drug-resistant multilobar onset epilepsy, who underwent intracranial video electroencephalography prior to multilobar resections. We measured the OR of HFOs and determined the electrodes with a high rate of HFOs by cluster analysis. We calculated MI, which reflects the degree of coupling between HFO (ripple/fast ripple [FR]) amplitude and 5 different frequency bands of delta and theta activities (0.5-1 Hz, 1-2 Hz, 2-3 Hz, 3-4 Hz, 4-8 Hz). In ES+ (n = 10), the OR(FRs) , the number of electrodes with high-rate FRs, and the MI(FRs & 3-4 Hz) in all electrodes were significantly higher than in ES- (n = 14). In both the ES+ and ES- groups, MI(ripples/FRs & 3-4 Hz) was the highest among the 5 frequency bands. Within the good seizure outcome group, the OR(FRs) and the MI(FRs & 3-4 Hz) in the resected area in ES+ were significantly higher than in ES- (OR[FRs] , P = .04; MI[FRs & 3-4 Hz] , P = .04). In ES+, the larger number of high-rate FR electrodes indicates more widespread epileptogenicity than in ES-. High values of OR(FRs) and MI(FRs & 3-4 Hz) in ES+ compared to ES- are a signature of the severity of epileptogenicity. We proved that ES+ children who achieved seizure freedom following multilobar resections exhibited strong coupling between slow oscillations and FRs.

Prevalence and patterns of anti-epileptic medication prescribing in the treatment of epilepsy in older adults with intellectual disabilities.

The prevalence of epilepsy is higher in people with intellectual disability (ID) and increases with the degree of ID. Although life expectancy for people with ID is increasing, people with ID coexisting with epilepsy have a higher mortality rate, particularly those who had recent seizures. There have been few observational studies of the prevalence and patterns of anti-epileptic prescribing among older people with ID and epilepsy. The aim of this study was to investigate prevalence and patterns of anti-epileptic prescribing in the treatment of epilepsy in a representative population of older people with ID and epilepsy. This was an observational cross-sectional study from wave 1 (2009/2010) of Intellectual Disability Supplement to the Irish Longitudinal Study on Aging, a nationally representative sample of 753 persons with ID aged between 41 and 90years. Participants and/or proxies recorded medicines used on a regular basis and reported doctor's diagnosis of epilepsy; medication data were available for 736 (98%). Prescribing of anti-epileptic drugs (AEDs) for epilepsy in those with a doctor's diagnosis of epilepsy (N=205) was the primary exposure of interest for this study. Participant exposure to these AEDs was then categorised into AED monotherapy and polytherapy. Participants/carers reported seizure frequency, when epilepsy was last reviewed and which practitioner reviewed epilepsy. In addition, medications that may lower the seizure threshold that were listed in the Maudsley prescribing guidelines in psychiatry were examined. Of the 736 participants with reported medicines use, 38.9% (n=287) were exposed to AEDs, and 30.6% (225) had a doctor's diagnosis of epilepsy. Of those with epilepsy (n=225), 90.9% (n=205) reported concurrent use of AEDs and epilepsy. Of these 205 participants, 50.3% (n=103) were exposed to AED polytherapy, and 63 different polytherapy regimes were reported. The most frequently reported AEDs were valproic acid (n=100, 48.7%), carbamazepine (n=89, 46.3%) and lamotrigine (n=57, 27.8%). In total, 13.7% had a concurrent psychotropic, which should be avoided in epilepsy, and 32.6% had a psychotropic where caution is required. Antipsychotics with potential epileptogenic potential accounted for 80% of these medications. Of those with AED polytherapy (n=103), 29.5% (28) reported being seizure free for the previous 2years. Prevalence of epilepsy was high among older people with ID, and half were exposed to two or more AEDs. Despite the use of AED therapy, over half had seizures in the previous 2years. As the primary goals of optimal AED treatment are to achieve seizure freedom without unacceptable adverse effects, this was not achievable for many older patients with ID and epilepsy. Our findings indicated that people with ID and epilepsy were often exposed to psychotropic medications that may lower the seizure threshold. Regular review of epilepsy and medicines (including medicines that may interact with AEDs or lower the seizure threshold) by multidisciplinary teams working to agreed standards may improve quality of prescribing. Improved exchange of information and coordination of care between specialists and primary care practitioners in line with expert consensus recommendations could bring substantial benefit.

Treatment Outcomes in Patients With Newly Diagnosed Epilepsy Treated With Established and New Antiepileptic Drugs

A study published in 2000 showed that more than one-third of adults with epilepsy have inadequate control of seizures with antiepileptic drugs (AEDs). This study evaluates overall treatment outcomes in light of the introduction of more than 1 dozen new AEDs in the past 2 decades. To assess long-term treatment outcome in patients with newly diagnosed and treated epilepsy. This longitudinal observational cohort study was conducted at the Epilepsy Unit of the Western Infirmary in Glasgow, Scotland. A total of 1795 individuals who were newly treated for epilepsy with AEDs between July 1, 1982, and October 31, 2012, were included in this analysis. All patients were followed up for a minimum of 2 years (until October 31, 2014) or until death, whichever came sooner. Data analysis was completed between March 2015 and May 2016. Treatment with antiepileptic drugs for patients newly diagnosed with epilepsy. Seizure control was assessed at the end of the study period. Probability of achieving 1-year seizure freedom was estimated for each AED regimen prescribed. Multivariable models assessed the associations between risk factors and AED treatment outcome after adjustments were made for demographic and clinical characteristics. Of the 1795 included patients, 964 (53.7%) were male; the median age was 33 years (range, 9-93 years). At the end of the study period, 1144 patients (63.7%) had been seizure free for the previous year or longer. Among those achieving 1-year seizure freedom, 993 (86.8%) were taking monotherapy and 1028 (89.9%) had achieved seizure control with the first or second AED regimens. Of the total patient pool, 906 (50.5%) remained seizure free for 1 year or longer with the initial AED. If this AED failed, the second and third regimens provided an additional 11.6% and 4.4% likelihoods of seizure freedom, respectively. Only 2.12% of patients attained optimal seizure control with subsequent AEDs. Epilepsy that was not successfully controlled with the first AED had 1.73 times greater odds of not responding to treatment for each subsequent medication regimen (odds ratio, 1.73; 95% CI, 1.56-1.91; P < .001). Despite the availability of many new AEDs with differing mechanisms of action, overall outcomes in newly diagnosed epilepsy have not improved. Most patients who attain control do so with the first or second AED. The probability of achieving seizure freedom diminishes substantially with each subsequent AED regimen tried. More than one-third of patients experience epilepsy that remains uncontrolled.

Surgical outcome and predictive factors of epilepsy surgery in pediatric isolated focal cortical dysplasia

ObjectiveFocal cortical dysplasia (FCD) is a common cause of medically intractable epilepsy in children. Epilepsy surgery has been a valuable treatment option to achieve seizure freedom in these intractable epilepsy patients. We aimed to present long-term surgical outcome, in relation to pathological severity, and to assess predictive factors of epilepsy surgery in pediatric isolated FCD. MethodsWe retrospectively analyzed the data of 58 children and adolescents, with FCD International League Against Epilepsy (ILAE) task force classification types I and II, who underwent resective epilepsy surgery and were followed for at least 2 years after surgery. ResultsThe mean age at epilepsy onset was 4.3 years (0–14.2 years), and mean age at epilepsy surgery was 9.4 years (0.4–17.5 years). The mean duration of postoperative follow-up was 5.1±2.6 years (2–12.4 years). Of 58 patients, 62% of patients achieved Engel class I at 2 years postoperatively, 58% at 5 years postoperatively, and 53% at the last follow up. Forty eight percent of our cohort successfully discontinued antiepileptic medication. Of 30 patients with seizure recurrence, 83% of seizures recurred within 2 years after surgery. We observed that FCD type IIb was significantly associated with a better surgical outcome. At fifth postoperative year, 88% of FCD IIb patients were seizure free compared with 21% of type I and 57% of type IIa patients (P=0.043). By multivariate analysis, lesion on MRI (P=0.02) and complete resection (P<0.01) were the most important predictive factors for a seizure-free outcome. SignificanceEpilepsy surgery is highly effective; more than half of medically intractable epilepsy patients achieved seizure freedom after surgery. In addition, we found significant difference in surgical outcomes according to the ILAE task force classification. Lesion on MRI and complete resection were the most important predictive factors for favorable seizure outcome in isolated FCD patients.

Resection of high frequency oscillations predicts seizure outcome in the individual patient

High frequency oscillations (HFOs) are recognized as biomarkers for epileptogenic brain tissue. A remaining challenge for epilepsy surgery is the prospective classification of tissue sampled by individual electrode contacts. We analysed long-term invasive recordings of 20 consecutive patients who subsequently underwent epilepsy surgery. HFOs were defined prospectively by a previously validated, automated algorithm in the ripple (80–250 Hz) and the fast ripple (FR, 250–500 Hz) frequency band. Contacts with the highest rate of ripples co-occurring with FR over several five-minute time intervals designated the HFO area. The HFO area was fully included in the resected area in all 13 patients who achieved seizure freedom (specificity 100%) and in 3 patients where seizures reoccurred (negative predictive value 81%). The HFO area was only partially resected in 4 patients suffering from recurrent seizures (positive predictive value 100%, sensitivity 57%). Thus, the resection of the prospectively defined HFO area proved to be highly specific and reproducible in 13/13 patients with seizure freedom, while it may have improved the outcome in 4/7 patients with recurrent seizures. We thus validated the clinical relevance of the HFO area in the individual patient with an automated procedure. This is a prerequisite before HFOs can guide surgical treatment in multicentre studies.

Failed epilepsy surgery deserves a second chance

ObjectivesResective epilepsy surgery has been shown to have up to 70–80% success rates in patients with intractable seizure disorder. Around 20–30% of patients with Engel Classification III and IV will require reevaluation for further surgery. Common reasons for first surgery failures include incomplete resection of seizure focus, incorrect identification of seizure focus and recurrence of tumor. Patient and methodsClinical chart review of seventeen patients from a single adult comprehensive epilepsy program who underwent reoperation from 2007 to 2014 was performed. High resolution Brain MRI, FDG-PET, Neuropsychometric testing were completed in all cases in both the original surgery and the second procedure. Postoperative outcomes were confirmed by prospective telephone follow up and verified by review of the patient’s electronic medical records. Outcomes were classified according to the modified Engel classification system: Engel classes I and II are considered good outcomes. ResultsA total of seventeen patients (involving 10 females) were included in the study. The average age of patients at second surgery was 42 (range 23–64 years). Reasons for reoperation included: incomplete first resection (n=13) and recurrence of tumor (n=4). Median time between the first and second surgery was 60 months. After the second surgery, ten of the seventeen patients (58.8%) achieved seizure freedom (Engel Class I), in agreement with other published reports. Of the ten patients who were Engel Class I, seven required extension of the previous resection margins, while three had surgery for recurrence of previously partially resected tumor. ConclusionsWe conclude that since the risk of complications from reoperation is low and the outcome, for some, is excellent, consideration of repeat surgery is justified.

Аnalysis of antiepileptic therapy of epilepsy patients in Bishkek

Background: Most patients with epilepsy can achieve seizure freedom with adequate and timely appointed single AED. Need for rational polytherapy may occur in 30-50% of patients who failed to achieve a reduction in seizure frequency with monotherapy.

Efficacy and safety of antiepileptic drugs for refractory partial-onset epilepsy: a network meta-analysis.

The optimal combination of antiepileptic drugs (AEDs) for the treatment of refractory partial-onset epilepsy is a perpetual point of debate. While several network meta-analyses (NMAs) have been published, conclusions remain controversial, especially since newer AEDs have been introduced. In our review, we included the newer AEDs to evaluate the comparative efficacy and safety of AEDs for the treatment of refractory partial-onset epilepsy. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials (Cochrane Library 2017, Issue 1) from their inception to February 18, 2017. The risk of bias in the included randomized controlled trials (RCTs) was evaluated according to the Cochrane Collaboration's risk of bias tool. An NMA was performed with a Bayesian random-effects model, and we used the surface under the cumulative ranking curve to detect the optimal AEDs. Seventy-six RCTs with 17 AEDs and 20,711 patients were included in the NMAs, which showed that Brivaracetam (BRV), Levetiracetam (LEV), Oxcarbazepine (OXC), Topiramate, Vigabatrin (VGB), and Valproate (VPA) had a greater likelihood of allowing patients to achieve seizure freedom. We also found that LEV was associated with a lower withdrawal rate due to adverse effects than Lacosamide, Eslicarbazepine acetate, OXC, Pregabalin, and Retigabine. LEV, VGB, VPA, and BRV emerged as the agents with the best combination of properties when considering the efficacy and safety outcomes based on the full double-blind treatment period. However, it is critical to perform RCTs and to obtain prospective data from representative cohort studies.