Decrease In Seizure Frequency Research Articles

Surgical management of medically refractory epilepsy in patients with polymicrogyria.

Polymicrogyria (PMG) is a malformation of cortical development characterized by formation of an excessive number of small gyri. Sixty percent to 85% of patients with PMG have epilepsy that is refractory to medication, but surgical options are usually limited. We characterize a cohort of patient with polymicrogyria who underwent epilepsy surgery and document seizure outcomes. A retrospective study of all patients with PMG who underwent epilepsy surgery (focal seizure foci resection and/or hemispherectomy) at our center was performed by review of all clinical data related to their treatment. We identified 12 patients (7 males and 5 female) with mean age of 18 (ranging from 3 months to 44 years) at time of surgery. Mean age at seizure onset was 8 years, with the majority (83%) having childhood onset. Six patients had focal, five had multifocal, and one patient had diffuse PMG. Perisylvian PMG was the most common pattern seen on magnetic resonance imaging (MRI). Eight patients had other cortical malformations including hemimegalencephaly and cortical dysplasia. Scalp electroencephalography (EEG) often showed diffuse epileptic discharges that poorly lateralized but were focal on intracranial electrocorticography (ECoG). Eight patients underwent seizure foci resection and four underwent hemispherectomy. Mean follow-up was 7 years (ranging from one to 19 years). Six patients (50%) were seizure-free at last follow-up. One patient had rare seizures (Engel class II). Three patients were Engel class III, having either decreased seizure frequency or severity, and two patients were Engel class IV. Gross total resection of the PMG cortex trended toward good seizure control. Our study shows that even in patients with extensive or bilateral PMG malformations, some may still be good candidates for surgery because the epileptogenic zone may involve only a portion of the malformation. Intracranial ECoG can provide additional localizing information compared to scalp EEG in guiding resection of epileptogenic foci.

Translational approach for gene therapy in epilepsy: Model system and unilateral overexpression of neuropeptide Y and Y2 receptors

Although novel treatment strategies based on the gene therapy approach for epilepsy has been encouraging, there is still a gap in demonstrating a proof-of-concept in a clinically relevant animal model and study design. In the present study, a conceptually novel framework reflecting a plausible clinical trial for gene therapy of temporal lobe epilepsy was explored: We investigated (i) whether the post intrahippocampal kainate-induced status epilepticus (SE) model of chronic epilepsy in rats could be clinically relevant; and (ii) whether a translationally designed neuropeptide Y (NPY)/Y2 receptor-based gene therapy approach targeting only the seizure-generating focus unilaterally can decrease seizure frequency in this chronic model of epilepsy.Our data suggest that the intrahippocampal kainate model resembles the disease development of human chronic mesial temporal lobe epilepsy (mTLE): (i) spontaneous seizures originate in the sclerotic hippocampus; (ii) only a part of the animals develops chronic epilepsy; (iii) animals show largely variable seizure frequency that (iv) tends to progressively increase over time. Despite significant hippocampal degeneration caused by the kainate injection, the use of MRI allowed targeting the recombinant adeno-associated viral (rAAV) vectors encoding NPY and Y2 receptor genes to the remaining dorsal and ventral hippocampal areas ipsilateral to the kainate injection. Continuous video-EEG monitoring demonstrated not only prevention of the progressive increase in seizure frequency in rAAV-NPY/Y2 treated animals as compared to the controls, but even 45% decrease of seizure frequency in 80% of the epileptic animals.This translationally designed study in a clinically relevant model of epilepsy suggests that simultaneous overexpression of NPY and Y2 receptors unilaterally in the seizure focus is a relevant and promising approach that can be further validated in more extensive preclinical studies to develop a future treatment strategy for severe, often pharmacoresistant focal epilepsy cases that cannot be offered alternative therapeutic options.

Stiripentol for focal refractory epilepsy.

This is an updated version of the original Cochrane review published in 2014 (Issue 1). For nearly 30% of people with epilepsy, seizures are not controlled by current treatments. Stiripentol is a new antiepileptic drug (AED) that was developed in France and was approved by the European Medicines Agency (EMA) in 2007 for the treatment of Dravet syndrome as adjunctive therapy with valproate and clobazam, with promising effects. To evaluate the efficacy and tolerability of stiripentol as add-on treatment for patients with focal refractory epilepsy who are taking AEDs. We searched the Cochrane Epilepsy Group Specialised Register (10 August 2015), the Cochrane Central Register of Controlled Trials (CENTRAL; August 2015, Issue 8)and MEDLINE (Ovid) (1946 to 10 August 2015). We contacted Biocodex (the manufacturer of stiripentol) and epilepsy experts to identify published, unpublished and ongoing trials. Randomised controlled add-on trials of stiripentol in patients with focal refractory epilepsy. Review authors independently selected trials for inclusion and extracted data. Outcomes investigated included 50% or greater reduction in seizure frequency, seizure freedom, adverse effects, treatment withdrawal and changes in quality of life. On the basis of our selection criteria, we included no new studies in the present review. However, we did include one study from the earlier review (32 children with focal epilepsy). This study adopted a 'responder enriched' design and found no clear evidence of a reduction in seizure frequency (≥ 50% seizure reduction) (risk ratio (RR) 1.51, 95% confidence interval (CI) 0.81 to 2.82) nor evidence of seizure freedom (RR 1.18, 95% CI 0.31 to 4.43) when add-on stiripentol was compared with placebo. Stiripentol led to a greater risk of adverse effects considered as a whole (RR 2.65, 95% CI 1.08 to 6.47). When specific adverse events were considered, confidence intervals were very wide and showed the possibility of substantial increases and small reductions in risks of neurological (RR 2.65, 95% CI 0.88 to 8.01) or gastrointestinal adverse effects (RR 11.56, 95% CI 0.71 to 189.36). Researchers noted no clear reduction in the risk of study withdrawal (RR 0.66, 95% CI 0.30 to 1.47), which was high in both groups (35.0% in add-on placebo and 53.3% in stiripentol group). The external validity of this study was limited because only responders to stiripentol (i.e. patients experiencing a ≥ 50% decrease in seizure frequency compared with baseline) were included in the randomised add-on placebo-controlled double-blind phase. Furthermore, carry-over and withdrawal effects probably influenced outcomes related to seizure frequency. Very limited information derived from the only included study shows that adverse effects considered as a whole seemed to occur significantly more often with add-on stiripentol than with add-on placebo. Since the last version of this review was published, we have found no new studies. Hence, we have made no changes to the conclusions of this update as presented in the initial review. We can draw no conclusions to support the use of stiripentol as add-on treatment for focal refractory epilepsy. Additional large, randomised, well-conducted trials are needed.

Cognition and behavior in a prevalent cohort of children with epilepsy in rural northern Tanzania: A three-year follow-up study.

Eighty-five percent of the 33 million children with epilepsy (CWE) worldwide live in low- and middle-income countries (LMICs). There is limited research into epilepsy-related comorbidities in LMICs, and there are no studies of the long-term progression of behavioral and intellectual difficulties in childhood epilepsy in sub-Saharan Africa. We aimed to assess behavior and cognition at three-year follow-up in CWE in rural Tanzania. In 2010, a cross-sectional study identified 112 CWE 6 to 14years of age and 113 age- and sex-matched controls in the Hai district of northern Tanzania. From March to June 2013, cases and controls (now 10 to 18years of age) were followed up. At baseline, behavior was assessed using the Rutter A Questionnaire and cognition using the Goodenough-Harris Drawing Test. Details of current seizure frequency and antiepileptic drug (AED) use among CWE were collected. At follow-up, cases had significantly more behavioral difficulties compared with controls (48% of 108 cases versus 14% of 103 controls (p<0.001)). Additionally, 69% of the cases and 16% of the controls had cognitive impairment (p<0.001). In CWE with decreased seizure frequency from baseline to follow-up, behavior had improved significantly. At follow-up, there was no significant difference in behavior between CWE with decreased seizure frequency and those with good seizure control throughout. Behavioral difficulties and cognitive impairment are common among CWE in this population. Improved access to AED treatment and subsequent improved seizure control may reduce the frequency of behavioral difficulties seen in this population.

Polyunsaturated fatty acids in children with idiopathic intractable epilepsy: Serum levels and therapeutic response

We aimed to assess serum levels of polyunsaturated fatty acids (PUFAs) and therapeutic response to omega 3 PUFAs supplementation in children with idiopathic intractable epilepsy. The study was done between November 2007 and December 2008 in the pediatric neurology clinic of Ain Shams University hospitals, Cairo. It comprised 20 children with idiopathic intractable epilepsy on antiepileptic drug polytherapy and twenty healthy age and sex matched controls. Serum levels of alpha-linolenic acid (ALA) (omega-3), eicosapentaenoic acid (EPA) (omega-3), docosapentaenoic acid (DPA) (omega-3), decosahexaenoic acid (DHA) (omega-3), linoleic acid (LA) (omega-6) and arachidonic acid (omega-6) were assessed by gas liquid chromatography. Prior to oral PUFAs supplementations, patients with intractable epilepsy had lower levels of DHA, DPA and higher levels of ALA, EPA and LA compared to controls. After 6 months of oral PUFAs supplementation, compared with healthy controls, levels of DHA was increased while, ALA, LA, EPA, DPA and arachidonic acid were decreased; while comparing to levels before supplement; furthermore, there were an increase in levels of DHA, DPA as well as DHA: EPA and LA: ALA ratios and a decrease in ALA, LA and EPA levels in patients following supplementation compared to their levels prior to oral supplementation. Both the changes in serum levels of PUFAs and their ratios were accompanied by decrease in seizure frequency, duration and severity. There was a significant negative correlation between serum DHA level and seizure duration as well as seizure severity. Altered serum levels of omega three and six PUFAs were associated with uncontrolled seizures, and oral supplementation with DHA and EPA lead to better seizure control.

Cerebral Arteriovenous Malformations and Epilepsy, Part 2: Predictors of Seizure Outcomes Following Radiosurgery

Seizure outcomes after arteriovenous malformation (AVM) management with radiosurgery are incompletely understood. In this case-control study, we aim to determine the incidences and define the predictors of seizure improvement and de novo seizures in patients with AVM with and without seizures at presentation, respectively. We evaluated our institutional AVM radiosurgery database to determine the factors that were associated with favorable seizure outcome (seizure improvement or lack of de novo seizures). In patients with seizures at presentation, seizure improvement was defined as decreased seizure frequency or complete seizure remission. In patients without seizures at presentation, de novo seizures were defined as new-onset seizures after radiosurgery. Logistic regression analyses were performed to identify predictors of favorable seizure outcome. In 229 patients with seizures at presentation, the rates of seizure improvement and seizure remission were 57% and 20%, respectively. Prior AVM hemorrhage (P = 0.015), longer follow-up (P < 0.0001), and lack of hemorrhage after radiosurgery (P = 0.048) were independent predictors of seizure improvement in the multivariate analysis. In 778 patients without seizures at presentation, the overall rate of de novo seizures was 1.7%. Prior AVM hemorrhage (P = 0.001) and higher Spetzler-Martin grade (P = 0.018) were independent predictors of the absence of de novo seizures in the multivariate analysis. AVM obliteration was not significantly associated with seizure outcomes after radiosurgery. Radiosurgery provides reasonable rates of seizure improvement for patients with AVM who present with seizures. For patients with AVM without seizures at presentation, the risk of de novo seizures after radiosurgery is very low, obviating the need for prophylactic antiepileptic drug therapy. Further investigation of epilepsy in patients with AVM undergoing stereotactic radiosurgery should be considered with validated outcome measures and prospective study design.

The long-term effect of vagus nerve stimulation on quality of life in patients with pharmacoresistant focal epilepsy: The PuLsE (Open Prospective Randomized Long-term Effectiveness) trial

Objective To evaluate whether vagus nerve stimulation (VNS) as adjunct to best medical practice (VNS + BMP) is superior to BMP alone in improving long-term health-related quality of life (HRQoL). Methods PuLsE (Open Prospective Randomized Long-term Effectiveness) was a prospective, randomized, parallel-group, open-label, and long-term effectiveness study (conducted at 28 sites in Europe and Canada). Adults with pharmacoresistant focal seizures (n = 112) received VNS + BMP or BMP (1:1 ratio). Medications and VNS parameters could be adjusted as clinically indicated for optimal seizure control while minimizing adverse effects. Primary endpoint was mean change from baseline HRQoL (using Quality of Life in Epilepsy Inventory-89 total score; QOLIE-89). Secondary endpoints included changes in seizure frequency, responder rate (≥50% decrease in seizure frequency), Centre for Epidemiologic Studies Depression scale (CES-D), Neurological Disorders Depression Inventory-Epilepsy scale (NDDI-E), Clinical Global Impression-Improvement scale (CGI-I), Adverse Event Profile (AEP), and antiepileptic drug (AED) load. The study was prematurely terminated due to recruitment difficulties prior to completing the planned enrollment of n = 362. Results for n = 96 who had baseline and at least one follow-up QOLIE-89 assessment (from months 3-12) were included in this analysis. Mixed model repeated measures (MMRM) analysis of variance was performed on change from baseline for the primary and secondary endpoints.

Seizures Outcome After Stereoelectroencephalography-Guided Thermocoagulations in Malformations of Cortical Development Poorly Accessible to Surgical Resection

Radiofrequency thermocoagulation (RFTC) guided by stereoelectroencephalography (SEEG) has proved to be a safe palliative method to reduce seizure frequency in patients with drug-resistant partial epilepsy. In malformation of cortical development (MCD), increasing the number of implanted electrodes over that needed for mapping of the epileptogenic zone could help to maximize RFTC efficiency. To evaluate the benefit of SEEG-guided RFTC in 14 patients suffering from drug-resistant epilepsy related to MCD located in functional cortical areas or in regions poorly accessible to surgery. Ten men and 4 women were treated by RFTC. Thermolesions were produced by applying a 50-V, 120-mA current for 10 to 30 seconds within the epileptogenic zone as identified by the SEEG investigation. An average of 25.8 ± 17.5 thermolesions were made per procedure. The median follow-up after the procedure was 41.7 months. Sixty-four percent of the patients experienced a long-term decrease in seizure frequency of >50%, of whom 6 (43%) presented long-lasting freedom from seizure. When a focal low-voltage fast activity was present at seizure onset on SEEG recordings, 87.5% of patients were responders or seizure free. All of the patients in whom electric stimulation reproduced spontaneous seizures were responders. Our results show the good benefit-risk ratio of the SEEG-guided procedure for patients suffering from MCD in whom surgery is risky. This study identifies 2 factors, focal low-voltage, high-frequency activity at seizure onset and lowered epileptogenic threshold in the coagulated area, that could be predictive of a favorable seizure outcome after RFTC.

Antiepileptic drugs in Rett Syndrome.

We investigated drugs most often used to treat epilepsy in Rett Syndrome and their efficacy in a large cohort of Italian patients. This is a multi-centre retrospective study. Data of 165 Rett subjects were collected from the patients' files, and hospital charts. The efficacy of antiepileptic drugs (AEDs) was classified as follows: not effective; decrease in seizure frequency ≥50% for at least 6 months; seizure-free for at least 2 years. Phenotypic and genetic categorization of patients was performed and it was considered in AEDs efficacy evaluation. There were 130 epileptic patients.Sodium valproate (VPA) was the most commonly administered AED (44.3%) at seizure onset, followed by Carbamazepine (CBZ) (25.4%) and Phenobarbital (PB) (13%). Monotherapy was the first treatment option in most patients. VPA and CBZ proved to be equally effective in Rett patients who presented seizures within the typical age range (4-5 years), while Lamotrigine (LTG) was effective for patients in whom epilepsy started later. Overall, the frequency of side effects was low and the most often observed ones were restlessness and somnolence. Our study suggests that LTG, VPA and CBZ can be used as drugs of first choice in Rett Syndrome. The association of four drugs should be avoided since it did not result in any significant clinical improvement.

Changes in background electroencephalography and regional cerebral glucose metabolism in focal epilepsy patients after 1-month administration of levetiracetam.

The antiseizure efficacy and safety of levetiracetam (LEV) is well documented; however, few clinical studies have investigated the predictability of patient responsiveness to LEV, especially when the drug is first administered. The aim of this study was to ascertain the utility of clinical, electrophysiological, and neuroimaging parameters for assessing the early response to LEV treatment in focal epilepsy patients. Twelve confirmed focal epilepsy patients were included who had never taken LEV before. At baseline and 1 month after LEV administration, all subjects underwent 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and electroencephalography (EEG), and completed the Quality of Life in Epilepsy questionnaire (QOLIE-31). Participants were divided by drug response: good versus poor. The good response group (seven subjects) was defined by a >50% decrease in seizure frequency compared to baseline (3 months before LEV intake). The other five participants with a <50% decrease in seizure frequency were placed into the poor response group. We compared the differential changes in brain glucose metabolism on FDG-PET, power spectrum on the EEG, and QOLIE-31 results between the two groups after a 1-month LEV trial. In the good response group, it was possible to identify brain regions with increased glucose metabolism, including the bilateral caudate nuclei and both frontal and left parietal regions (uncorrected P<0.005). In the poor response group, FDG-PET did not reveal any areas with significantly increased glucose metabolism. In the good response group, spectral EEG analysis revealed decreased delta power (1–3 Hz, P<0.05) in the parietal region and increased beta1 power (13–19 Hz, P<0.05) in the frontal region, whereas no significant changes were observed in the poor response group. There were no significant changes on the QOLIE-31 in either group after a 1-month LEV trial. Our results suggest that LEV-induced glucose metabolism and EEG spectral changes may be indicative of initial drug responsiveness as early as 1 month following treatment initiation. These parameters may be useful prognostic markers of antiseizure effects caused by LEV medication or may indicate an epiphenomenon of LEV-induced changes in glucose metabolism and EEG frequency. Further studies with larger sample sizes are warranted.

Effect of licorice flavonoids on kainic acid-induced seizure in mice

To investigate the effect of licorice flavonoid (LF) on kainic acid (KA)-induced seizure in mice and its mechanism. Male adult ICR mice were injected with 25 mg/kg KA to induce temporal lobe seizure. LF was administrated 7 d before seizure induction (pre-treatment) or 24 h after seizure induction (post-treatment) for 7 d. Acute seizure latency, seizure stage and duration were observed and compared between LF- and vehicle-treated mice. From d2 on, mice with status epilepticus were video-monitored for spontaneous seizures, 10 h/d for 6 w. Immunohistochemical analysis of BrdU and Timm staining was conducted to detect the neurogenesis and mossy fiber sprouting, respectively. No significant difference was observed in acute seizure latency, seizure stage and duration between LF-and vehicle-treated mice. KA-induced acute seizure resulted in spontaneous seizure in mice, and the seizure frequency was increased with time. Pre- and post-treatment with LF decreased seizure frequency from w3 after modeling [(0.58±0.15)/d, (0.38±0.38)/d vs (1.23±0.23)/d, P <0.05]. Furthermore, KA-induced seizure resulted in robust neurogenesis and mossy fiber sprouting, while treatment with LF both pre- and post- KA injection significantly inhibited neurogenesis (15.6±2.6, 17.1±3.1 vs 28.9±3.5, P <0.05) and mossy fiber sprouting (1.33±0.31, 1.56±0.42 vs 3.0±0.37, P <0.05). LF has no significant anti-seizure effect. However, it can decrease epileptogenesis through inhibition of neurogenesis and mossy fiber sprouting.

Clinical utility of implantable neurostimulation devices as adjunctive treatment of uncontrolled seizures.

About one third of patients with epilepsy are refractory to medical treatment. For these patients, alternative treatment options include implantable neurostimulation devices such as vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation systems (RNS). We conducted a systematic literature review to assess the available evidence on the clinical efficacy of these devices in patients with refractory epilepsy across their lifespan. VNS has the largest evidence base, and numerous randomized controlled trials and open-label studies support its use in the treatment of refractory epilepsy. It was approved by the US Food and Drug Administration in 1997 for treatment of partial seizures, but has also shown significant benefit in the treatment of generalized seizures. Results in adult populations have been more encouraging than in pediatric populations, where more studies are required. VNS is considered a safe and well-tolerated treatment, and serious side effects are rare. DBS is a well-established treatment for several movement disorders, and has a small evidence base for treatment of refractory epilepsy. Stimulation of the anterior nucleus of the thalamus has shown the most encouraging results, where significant decreases in seizure frequency were reported. Other potential targets include the centromedian thalamic nucleus, hippocampus, cerebellum, and basal ganglia structures. Preliminary results on RNS, new-generation implantable neurostimulation devices which stimulate brain structures only when epileptic activity is detected, are encouraging. Overall, implantable neurostimulation devices appear to be a safe and beneficial treatment option for patients in whom medical treatment has failed to adequately control their epilepsy. Further large-scale randomized controlled trials are required to provide a sufficient evidence base for the inclusion of DBS and RNS in clinical guidelines.

Factors associated with superior self-management skills among individuals with epilepsy

PurposeThis study aimed to determine whether the self-management skills of patients with epilepsy are associated with certain demographic, clinical, and psychosocial variables. MethodsA direct survey of 182 patients, including the Epilepsy Self-Management Scale, was conducted. ResultsOn univariate analysis, higher age, the occurrence of convulsions, and the use of religion as a coping mechanism were associated with higher self-management scores. On multiple linear regression, only age and the presence of convulsions remained independently significant. Older individuals employed more medication management skills. Those who experienced convulsions utilized more information management, seizure management, and lifestyle management skills. However, using binary logistic regression, we found that these subscales were not independently significant.The presence of superior self-management skills did not necessarily translate into decreased seizure frequency. ConclusionIndividuals with epilepsy who are older and experience convulsions generally have better self-management skills. This indicates that antecedents influence the development of self-management skills.

O9.09 * EFFICACY AND TOLERABILITY OF LACOSAMIDE IN PATIENTS WITH GLIOMA: A PROSPECTIVE STUDY

BACKGROUND: Lacosamide (LCM) has been suggested in some retrospective studies to improve seizure control as an add-on treatment in brain tumor patients. We present here the preliminary results of a prospective study focused on a cohort of patients with gliomas and active epilepsy who received LCM. METHODS: Eligibility criteria were as follows: 1) biopsy-proven grade II or III or IV gliomas according to WHO 2007; 2) persisting seizures (seizure frequency > 1 per month) despite a treatment with 1 or more antiepileptic drugs (AEDs) for at least 3 months and adequate serum concentration; 3) stable steroid dose; 4) available information on tumor response on MRI according to RANO criteria following chemotherapy or radiotherapy; 5) age > 18 years. LCM was given at 50 mg daily for one week with an increase of 50 mg twice daily every week to a target dose of 200-400 mg/day. The endpoints were > 50% decrease of seizure frequency and seizure freedom at 3 and 6 months. RESULTS: Since January 2012 42 patients were enrolled. There were 17 grade II gliomas (5 astrocytomas, 8 oligodendrogliomas, 4 oligoastrocytomas), 13 grade III (4 astrocytomas, 3 oligodendrogliomas, 6 gliomatosis cerebri) and 12 glioblastomas. Ten patients (23.8%) had generalized seizures and 32 (76.2%) partial seizures. Thirty-six patients (85.7%) were on AED monotherapy while 6 (14.3%) on polytherapy. Reasons for introduction of LCM were unacceptable side effects of traditional AEDs in 5 patients (12%) and/or lack of efficacy of previous AEDs associated with either PD in 16 (38%) or without PD in 26 (62%). Median duration of follow up was 6.6 months (range 3-24 months). Among low grade gliomas after 3 months of LCM 5/17 patients (29.4%) had a reduction of >50% of seizure frequency while seizure freedom was obtained in other 3/17 (17.6%); at 6 months a reduction of >50% of seizure frequency was observed in 5 (29.4%) while seizure freedom was obtained in other 2 (11.8%) for overall seizure control of 41.2%. As for high grade gliomas after 3 months 6/25 patients (24%) had a reduction of >50% of seizure frequency while seizure freedom was obtained in other 11/25 (44%); at 6 months a reduction of >50% of seizure frequency was observed in 7/22 (31.8%) and seizure freedom in other 6 (27.3%) for overall seizure control of 59.1% . A resolution of an epileptic status was obtained in 3 patients of whom one receveing LCM alone. Secondary generalized seizures disappeared in 4 patients. However, responding patients were not able to reduce the doses of previous AEDs. Most patients (97.6%) did not report significant toxicities: in 2 cases only LCM was withdrawn due to dizziness and fatigue and resistant epilepsy, respectively. CONCLUSION: Among patients both with high grade and low grade gliomas LCM is well tolerated without interactions with antitumoral treatments. LCM shows significant activity as add-on therapy regardless of tumor response to antineoplastic treatment.

Sustained reduction of seizures in patients with intractable epilepsy after self-regulation training of slow cortical potentials - 10 years after.

The aim of this study was to determine whether the reduction of seizures in patients with intractable epilepsy after self-regulation of slow cortical potentials (SCPs) was maintained almost 10 years after the end of treatment. Originally, 41 patients received training with SCP-neurofeedback. A control group of 12 patients received respiratory feedback while another group of 11 patients had their anticonvulsant medications reviewed. Nineteen patients in the experimental group participated at least in parts of the long-term follow-up, but only two patients from each control group agreed to do so. The follow-up participants completed the same seizure diaries as in the original study. Patients of the experimental group also took part in three SCP-training sessions at the follow-up evaluation. Due to the small sample size, the results of participants in the control groups were not considered in the analysis. A significant decrease in seizure frequency was found about 10 years after the end of SCP treatment. The clinical significance of this result is considered medium to high. All patients were still able to self-regulate their SCPs during the feedback condition. This success was achieved without booster sessions. This is the longest follow-up evaluation of the outcome of a psychophysiological treatment in patients with epilepsy ever reported. Reduced seizure frequency may be the result of patients continued ability to self-regulate their SCPs. Given such a long follow-up period, the possible impact of confounding variables should be taken into account. The small number of patients participating in this follow-up evaluation diminishes the ability to make causal inferences. However, the consistency and duration of improvement for patients who received SCP-feedback training suggests that such treatment may be considered as a treatment for patients with intractable epilepsy and as an adjunct to conventional therapies.

Experience of Using Vagus Nerve Stimulation to Treat Drug Resistant Epilepsy

Objective. To determine tolerability and effectiveness of continuous vagus nerve stimulation (VNS) in patients with drug resistance epilepsy (DRE). Patients and Methods. A VNS system was implanted to 9 adults (aged 14–38) with DRE. The duration of catamnesis was 8–12 months. Results. During the first 2–3 months after the VNS system had been implanted, seizure frequency reduced by over 50% in half of the patients with DRE. The remaining patients showed a similar positive effect 8–12 months after the VNS parameters had been adjusted. A decrease in seizure frequency, duration and severity, as well as shortening of the post-seizure period were observed in 12.5% of patients. Negative side effects, such as dysphonia and throat discomfort, were found in 12.5% of patients. These undesirable effects were eliminated by adjusting magnetic stim- ulation parameters. Significant positive EEG dynamics, such as regression of paroxysmal epileptic activity, were obtained in 62.5% the cases. Conclusions. VNS therapy is a safe and effective treatment method for reducing the frequency and severity of seizures in patients with DRE.

Effectiveness of Epilepsy Therapy in Adults after Correction Performed by an Epileptologist

Objective. To optimize the therapeutic and preventive care for epilepsy patients based on the results of examination and therapy correction performed by an epileptologist. Patients and Methods. Results of clinico-epidemiological examination of 587 adult patients with epilepsy (320 males and 267 females) are presented. The effectiveness of the antiepileptic therapy before and after it had been optimized by an epileptologist was analyzed. Results. The results demonstrated that optimization of antiepileptic drug therapy according to the recommendations of the International League Against Epilepsy (ILAE) allowed 91.87% of patients to achieve positive result: the termination of seizures was observed in 66.61% of cases; a decrease in seizure frequency by over 50% was observed in 25.26% of cases. A total of 6.26% of patients showed clinical improve- ment (seizure frequency was reduced by less than 50%). The therapy turned out to be inefficient in 1.87% of patients.

Seizure Control Following Palliative Resective Surgery for Intractable Epilepsy—A Pilot Study

BackgroundPatients with intractable epilepsy who have bilateral epileptic foci may not qualify for curative epilepsy surgery. In some cases palliative resection may be undertaken with a goal to decrease seizure frequency and improve quality of life. Here we present data on the outcome of palliative epilepsy surgery in children. MethodsWe reviewed medical charts of children who underwent palliative resection for intractable epilepsy during the years 1999-2013 at Children's Hospital of Michigan. The palliative intent of resection was declared preoperatively. Outcome was assessed in terms of seizure reduction. ResultsThere were 18 patients (11 males, median age of surgery was 3.5 years [range 0.5-16 years]). The median duration of follow-up after surgery was 12.5 months (range 6-60 months). Hemispherectomy was the most commonly performed palliative resection (nine patients), followed by lobectomy (six patients), multilobar resection (one patient), and tuberectomy (two patients). Reduction in seizure frequency was observed in 11 patients, with eight patients achieving seizure freedom on antiepileptic drugs and three with >50% reduction in seizure frequency. Transient improvement in seizure frequency occurred in two patients, whereas there was no benefit in five patients. ConclusionsBeneficial effects of epilepsy surgery may be realized in carefully selected situations wherein the most epileptogenic focus is resected to reduce seizure burden and improve quality of life.

The long-term effect of vagus nerve stimulation on quality of life in patients with pharmacoresistant focal epilepsy: the PuLsE (Open Prospective Randomized Long-term Effectiveness) trial.

ObjectiveTo evaluate whether vagus nerve stimulation (VNS) as adjunct to best medical practice (VNS + BMP) is superior to BMP alone in improving long-term health-related quality of life (HRQoL).MethodsPuLsE (Open Prospective Randomized Long-term Effectiveness) was a prospective, randomized, parallel-group, open-label, and long-term effectiveness study (conducted at 28 sites in Europe and Canada). Adults with pharmacoresistant focal seizures (n = 112) received VNS + BMP or BMP (1:1 ratio). Medications and VNS parameters could be adjusted as clinically indicated for optimal seizure control while minimizing adverse effects. Primary endpoint was mean change from baseline HRQoL (using Quality of Life in Epilepsy Inventory-89 total score; QOLIE-89). Secondary endpoints included changes in seizure frequency, responder rate (≥50% decrease in seizure frequency), Centre for Epidemiologic Studies Depression scale (CES-D), Neurological Disorders Depression Inventory-Epilepsy scale (NDDI-E), Clinical Global Impression-Improvement scale (CGI-I), Adverse Event Profile (AEP), and antiepileptic drug (AED) load. The study was prematurely terminated due to recruitment difficulties prior to completing the planned enrollment of n = 362. Results for n = 96 who had baseline and at least one follow-up QOLIE-89 assessment (from months 3-12) were included in this analysis. Mixed model repeated measures (MMRM) analysis of variance was performed on change from baseline for the primary and secondary endpoints.ResultsSignificant between-group differences in favor of VNS + BMP were observed regarding improvement in HRQoL, seizure frequency, and CGI-I score (respective p-values < 0.05, 0.03, and 0.01). More patients in the VNS + BMP group (43%) reported adverse events (AEs) versus BMP group (21%) (p = 0.01), a difference reflecting primarily mostly transient AEs related to VNS implantation or stimulation. No significant difference between treatment groups was observed for changes in CES-D, NDDI-E, AEP, and AED load.SignificanceVNS therapy as a treatment adjunct to BMP in patients with pharmacoresistant focal seizures was associated with a significant improvement in HRQoL compared with BMP alone.

Stiripentol for the treatment of Dravet syndrome

Stiripentol (marketed by Biocodex as Diacomit ® ) is an anticonvulsant drug, structurally unrelated to any other compound, which has recently been approved as adjunctive therapy with clobazam and valproate for Dravet syndrome in Europe, Canada, and Japan. This rare form of early childhood epilepsy is associated with subsequent cognitive impairment, significant risk of death, and high pharmacoresistance. Based on an efficacy signal of stiripentol added to cloba - zam and valproate in an observational, prospectively conducted, exploratory study including 10% of children with Dravet syndrome, a randomized placebo-controlled trial was specifically dedicated to patients with Dravet syndrome inadequately controlled by clobazam and valproate. Results showed significantly higher responder rates (71% versus 5%; P,0.0001) and decrease in seizure frequency (-69% versus +7%; P,0.002) on stiripentol than on placebo. A second, independently performed, randomized controlled trial confirmed these results 2 years later, and both trials were plotted in a meta-analysis. Efficacy was supported by three subsequent obser - vational studies, with, respectively, 46 (France), 23 (Japan), and 82 (USA) children with Dravet syndrome treated with stiripentol for up to 5 years. Based on the experiences of more than 2,000 patients with Dravet syndrome who were exposed to stiripentol, drowsiness, loss of appetite, and weight loss are the most frequent adverse events and may be reduced by decreasing the dosage of co-medication. The inhibition of stiripentol by the cytochrome P450 complex (CYP2C19, and CYP3A4) leads to clinically significant interactions. Experimental data, both in vitro and in vivo, have definitively established that stiripentol is a GABAergic anticonvulsant and acts on different sites than benzodiazepines. The pharmacodynamic interactions also enhance the anticonvulsant effect of the stiripentol-clobazam combination in patients with Dravet syndrome, irrespective of the GABAergic effect. Stiripentol is currently the only drug specifically indicated in Dravet