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Objective: The aim of this study was to evaluate the efficacy, tolerability, and retention of brivaracetam (BRV) in genetic generalized epilepsy (GGE) in real-life practice., Methods: This is a retrospective cohort study of adult patients with GGE in whom BRV was started between 2016 and 2018, completing a follow-up period of ≥6 months. Clinical and electroencephalogram (EEG) characteristics were analyzed at baseline and at follow-up as outcome measures., Results: Brivaracetam was started in 37 patients (mean age: 29.9 ± 12.3 years; 73% women). Juvenile myoclonic epilepsy was the most common syndrome (43.2%). The primary indications for starting BRV were lack of efficacy (51.4%) and adverse events (AEs) (27%) of other antiepileptic drugs (AEDs). In total, 32.4% of patients received BRV monotherapy. Retention rate at 6 months was 81.1%; 83.8% of patients were considered responders, and 62.2% achieved seizure freedom. The primary reasons for withdrawal were treatment-emergent adverse events (TEAEs, 57.1%) and lack of efficacy (42.9%). The higher number of prior AED use was a risk factor for a lack of response [median = 4 (interquartile range (IQR): 3-4) vs 2 (IQR: 1-3); p < 0.05]. Patients with a previous response to valproic acid tended to have a higher response rate to BRV (86.7% vs 50%, p = 0.169). Eighty-three point eight percent (83.8%) of previous levetiracetam (LEV) responders also showed a good response to BRV. In terms of patients who presented LEV-related AEs, AE resolution was observed in 79.8%, particularly with regard to psychiatric AEs. Follow-up EEGs were compared with baseline EEGs in 25 patients (67.6%) during follow-up. Most patients showed a reduction (52%) or no change (36%) in interictal epileptiform discharge (IED) frequency., Significance: Brivaracetam shows good responder and retention rates in GGE and is generally well tolerated. It is an appropriate alternative treatment for GGE, especially in refractory epilepsy and when other AEDs are not tolerated., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: A number of antiepileptic drugs (AEDs) are currently available for treating acute seizures. It is recommended to select the initial treatment option according to the type of epileptic syndrome and the patient's clinical characteristics, but little is known about the long-term retention rates of AEDs started in the emergency department., Methods: We recruited patients admitted with seizures over a two-year period. All patients underwent early neurological assessment, EEG testing, and neuroimaging. The treatments received at baseline and at one year of follow-up were compared., Results: In total, 225 patients were included. Overall, monotherapy with levetiracetam was the regimen most often used in patients with new-onset seizures, whereas other AEDs were mainly used in patients previously treated with other drugs. Lacosamide use was most likely associated with the presence of lesion related seizures in elderly patients, and carboxamides with focal onset seizures of unknown cause. The mean retention rate of the total of AED treatments was nearly 70%. The main cause leading to discontinuation was the development of intolerable adverse events. Levetiracetam use decreased as lacosamide use increased in the overall group of patients., Conclusion: Our study shows that there is a trend to use newer AEDs, particularly levetiracetam, as the first option in new-onset seizures in the emergency room. However, levetiracetam use significantly decreased over follow-up, mainly because of the development of adverse events. The use of other, better-tolerated AEDs, such lacosamide predominated in elderly patients and patients with lesion related seizures, or carboxamides in epilepsies of unknown etiology., (Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objectives: To assess state and trait anger, adjusted by epilepsy type, seizure control, anxiety-depression status and quality of life, in patients treated with brivaracetam (BRV) from an open study., Methods: We evaluated prospectively consecutive patients with partial onset seizures in an open-label study. Patients had 5 years or longer of epilepsy and were taking between 1 and 3 antiepileptic drugs. They were treated with BRV and compared with a control group selected from outpatients attending our epilepsy unit who met the following criteria: age ≥16 years and diagnosis of epilepsy with focal-onset seizures at least 1 year before inclusion in the study. The following tests were assessed: State-Trait Anger with the Expression Inventory-2, Hospital Anxiety and Depression Scale, and Quality of Life in Epilepsy Inventory., Results: We recruited 39 patients, 17 treated with BRV and 22 with other drugs, including 13 with levetiracetam (LEV). Mean age was 47.3 years, 43.6% were men. Symptomatic cases, 66% and 52% temporal lobe epilepsy. Antiepileptic drug polytherapy was present in 82.1% of the cases (100% BRV vs 68.2% control group). Demographic and clinical characteristics, as well as Quality of Life in Epilepsy Inventory and Hospital Anxiety and Depression Scale scores were similar in both groups. When compared with the subgroup of LEV groups did not differ significantly on their Hospital Anxiety and Depression Scale scores., Conclusions: This small, open study suggests that BRV increases anger measures less than LEV in epilepsy patients. However, larger, blinded control studies are required to establish whether this apparent difference can be confirmed.

Background: Valproic acid (VPA) is an effective treatment in juvenile myoclonic epilepsy (JME), but concerns on its use during pregnancy are remarkable. Levetiracetam (LEV) is approved as second-line therapy, and used as monotherapy in clinical practice. Our objective was to analyze the outcome of LEV and VPA in JME., Materials and Methods: We analyzed patients with JME attending our epilepsy unit between 2010 and 2014, including all patients treated with LEV and/or VPA at some point of the disease course. The primary end point was drug retention rate in monotherapy after the final analysis., Results: We identified 58 patients (62% women). All had myoclonic seizures, 86% had generalized tonic-clonic seizures (GTCS) before the diagnosis, and 9% also had absences. All had generalized spike and wave on the interictal electroencephalogram, and 86% of them also had generalized polyspike and wave discharges. In total, LEV monotherapy was maintained in 15 (65%) of 23 patients, and VPA was maintained in 37 (74%) of 50 patients (P = 0.062). In women younger than 35 years, LEV had a similar retention rate with VPA (P = 0.939). More VPA patients achieved seizure freedom during follow-up (P < 0.01), whereas LEV patients showed a trend toward higher myoclonic freedom (0.085)., Conclusions: Levetiracetam showed lower retention rate than VPA, primarily due to poorer seizure control during long-term follow-up. More LEV patients achieved myoclonic seizure freedom than VPA patients. In women younger than 35 years, LEV and VPA had comparable retention rate; therefore, LEV could be a good option for women with JME with prominent myoclonic seizures.

Introduction: Prognosis in epilepsy refers to the probability of either achieving seizure remission (SR), whether spontaneously or using antiepileptic drugs (AED), or failing to achieve control of epileptic seizures (ES) despite appropriate treatment. Use of AED is recommended after a second unprovoked ES. For a first episode, the decision of whether or not to start drug treatment depends on the risk of recurrence and the advantages or disadvantages of the antiepileptic drug. The main goal of treatment is achieving absence of ES without adverse effects (AE). AED is selected according to epilepsy type and the demographic and clinical characteristics of the patient., Development: A PubMed search located articles and recommendations by the most relevant scientific societies and clinical practice guidelines concerning epilepsy prognosis and treatment. Evidence and recommendations are classified according to the prognostic criteria of the Oxford Centre for Evidence-Based Medicine (2001) and the European Federation of Neurological Societies (2004) for therapeutic actions., Conclusions: Most newly diagnosed epileptic patients achieve good control over their ES. The majority of the AEDs available at present provide effective control over all types of ES, and choice therefore depends on the patient's individual characteristics. Treatment should be initiated as monotherapy at the lowest effective dose, which in half of all patients provides ES control and is well tolerated. In cases in which the first AED is not effective, alternative therapy should be started, and monotherapy should be employed before combination therapy where possible. The probability of achieving good control over ES decreases with each successive treatment failure., (Copyright © 2014 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: We analyzed clinical and psychosocial factors in patients with refractory psychogenic nonepileptic seizures, seeking characteristics that could hasten diagnosis., Background: Psychogenic nonepileptic seizures remain a diagnostic challenge. Prognosis is best if patients are treated within 2 years of symptom onset. Psychosocial factors have been shown to provide important information for differential diagnosis., Methods: Over a year and 1132 consecutive patients, our hospital's Epilepsy Unit suspected 93 patients of having psychogenic nonepileptic seizures and confirmed refractory psychogenic nonepileptic seizures in 67. We referred these patients to our psychiatric consultation unit for detailed diagnostic interviews, and 53 of the patients followed through. Two months after the psychiatric evaluation we gave them a psychiatric intervention, explaining the diagnosis and treating their comorbidities. We also tracked the patients' use of antiepileptic drugs for 3 months, from just before the psychiatric evaluation until a month after they started the intervention., Results: Women, patients with an inadequate primary support group, and patients who had tried many antiepileptic drugs were most likely to have their diagnosis of psychogenic nonepileptic seizures delayed by >2 years after onset. A stepwise logistic regression showed that the 2 best predictors of late diagnosis were lack of availability of a primary support group and patients trying many antiepileptic drugs., Conclusions: Clinicians evaluating patients with questionable seizures should raise their suspicion of psychogenic nonepileptic seizures especially in female patients with an insufficient primary support group and a history of taking multiple antiepileptic drugs.

Inflammation is one of the most important endogenous defence mechanisms in an organism. It has been suggested that inflammation plays an important role in the pathophysiology of a number of human epilepsies and convulsive disorders, and there is clinical and experimental evidence to suggest that inflammatory processes within the CNS may either contribute to or be a consequence of epileptogenesis. This review discusses evidence from human studies on the role of inflammation in epilepsy and highlights potential new targets in the inflammatory cascade for antiepileptic drugs. A number of mechanisms have been shown to be involved in CNS inflammatory reactions. These include an inflammatory response at the level of the blood-brain barrier (BBB), immune-mediated damage to the CNS, stress-induced release of inflammatory mediators and direct neuronal dysfunction or damage as a result of inflammatory reactions. Mediators of inflammation in the CNS include interleukin (IL)-1β, tumour necrosis factor-α, nuclear factor-κB and toll-like receptor-4 (TLR4). IL-1β, BBB and high-mobility group box-1-TLR4 signalling appear to be the most promising targets for anticonvulsant agents directed at inflammation. Such agents may provide effective therapy for drug-resistant epilepsies in the future.

Objective: With the objective of evaluating the efficacy and tolerability of topiramate (TPM) in resistant epilepsy, we did a retrospective, open, multicentric analysis of 56 patients aged over 15 years in whom TPM was given as the second, third or fourth drug. All patients had already been on treatment for at least 18 months when topiramate was started. The average follow up was 27.2 months., Results: At the close of the study 16% of the patients were asymptomatic, 23% had a 75% reduction in seizures and 36% a 50% reduction. The drug was withdrawn in 25% of the cases. The adverse effects noted were: nephrolithiasis, asthenia, loss of hair, diarrhoea, weight loss of over 5kg., agitation, aggressiveness, language disorders, ataxia, tremor, somnolence and confusion. The drug had to be suspended when these adverse effects affected the central nervous system moderately or severely, and when there were general effects such as renal calculi in one case and weight loss associated with symptoms which worried the patients in two cases., Conclusions: Thus, TPM is an effective drug in refractory epilepsy and most patients continue on this treatment. The side effects are typical of the drug, and although there is no risk to life, the patient should be warned of them.

Recent studies by Isojärvi et al. have raised the issue of an increased incidence of polycystic ovary syndrome (PCOS) in women with epilepsy treated with valproate (VPA) and have proposed replacement with lamotrigine (LTG). Polycystic ovaries (PCO) are a common finding, with a prevalence >20% in the general population, and are easily detected by pelvic or vaginal ultrasonography, whereas PCOS is comparatively rare: few women with PCO have fully developed PCOS, which includes hirsutism, acne, obesity, hypofertility. hyperandrogenemia, and menstrual disorders. From an extensive review of the current literature, it appears that there are no reliable data on the actual prevalence of PCOS in normal women and in women with epilepsy. The pathogenesis of PCO is multifactorial, including genetic predisposition and the intervention of environmental factors, among which weight gain and hyperinsulinism with insulin resistance may play a part. The roles of central (hypothalamic/pituitary), peripheral, and local ovarian factors are still debated. PCO and PCOS appear to be more frequent in women with epilepsy, but there are no reliable data showing a greater prevalence after VPA. The recent studies by Isojärvi et al. may have been biased by the retrospective selection of patients. To date, there is no reason to contraindicate the use of VPA in women with epilepsy. However, patients should be informed about the risk of weight gain and its consequences.

Objective: To analyze the cost of monotherapeutic treatment of patients with newly diagnosed epilepsy., Patients and Methods: We analysed the cost of treatment with lamotrigine (LTG), carbamazepine (CBZ), phenytoin (PHT) and valproic acid (VPA) using published data regarding the efficacy and tolerability of comparative clinical trials of monotherapy. We established a model of treatment for newly diagnosed patients during the first 12 months after diagnosis. A panel of doctors reached a consensus on the use of resources, costs and model of treatment in Spain. We made a cost minimization analysis for economic assessment of the data based on the fact that randomized trials indicated that CBZ, LTG, PHT and VPA ware of similar efficacy. Analysis was done as 'intention to treat'. Only direct medical costs were considered., Results: In Spain treatment with LTG is twice or three times as expensive as treatment with the other drugs. Sensitivity analysis showed that variations in the interval of use of resources and of costs (defined by the panel of doctors) did not significantly alter the results., Conclusions: Treatment with LTG is more expensive than treatment with the classical drugs. In view of the methodological limitations of this study, further analysis is necessary, particularly of the methodology of cost-benefit, to evaluate the economic impact of the new antiepileptic drugs and determine whether their use is justified as drugs of first choice.