Pathways to epilepsy surgery in children with tuberous sclerosis complex-associated epilepsy.

BACKGROUND: Previous studies showed the efficacy of epilepsy surgery in carefully selected children with epilepsy associated with tuberous sclerosis complex. However, how this selection is conducted, and the characteristics of the patients brought to surgery are still poorly described. By conducting a multicentric retrospective cohort study covering the practice of the last twenty years, we describe the paths leading to epilepsy surgery in children with epilepsy associated with tuberous sclerosis complex. METHODS: We identified 84 children diagnosed with tuberous sclerosis complex and epilepsy by matching two exhaustive registries of genetic diseases and subsequent medical records reviews within two French neuropediatric and epilepsy centers. Demographic, clinical, longitudinal, and diagnostic and surgical procedures data were collected. RESULTS: Forty-six percent of the children were initially drug-resistant and 19% underwent resective surgery, most often before the age of four. Stereotactic electroencephalography was performed prior to surgery in 44% of cases. Fifty-seven and 43% of patients remained seizure-free one and ten years after surgery, respectively. In addition, 52% of initially drug-resistant patients who did not undergo surgery were seizure-free at the last follow-up. The number of anti-seizure medications required decreased in 50% of cases after surgery. Infantile spasms, intellectual disability, autism spectrum disorder or severe behavioral disorders were not contraindications to surgery but were associated with a higher rate of complications and a lower rate of seizure freedom after surgery. CONCLUSION: Despite the assumption of complex multifocal epilepsy and practical difficulties in young children with tuberous sclerosis complex, successful surgery results are comparable with other populations of patients with drug-resistant epilepsy, and a spontaneous evolution to drug-sensitive epilepsy may occur in non-operated patients.

Drug-resistant generalized epilepsies: Revisiting the frontiers of idiopathic generalized epilepsies.

The 2017 International League Against Epilepsy (ILAE) classification suggested that the term "genetic generalized epilepsies" (GGEs) should be used for the broad group of epilepsies with so-called "generalized" seizure types and "generalized" spike-wave activity on EEG, based on a presumed genetic etiology. Within this framework, idiopathic generalized epilepsies (IGEs) are described as a subset of GGEs and include only four epileptic syndromes: childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, and epilepsy with generalized tonic-clonic seizures alone. The recent 2022 ILAE definition of IGEs is based on the current state of knowledge and reflects a community consensus and is designed to evolve as knowledge advances. The term "frontiers of IGEs" refers to the actual limits of our understanding of these four syndromes. Indeed, among patients presenting with a syndrome compatible with the 2022 definition of IGEs, we still observe a significant proportion of patients presenting with specific clinical features, refractory seizures, or drug-resistant epilepsies. This leads to the discussion of the boundaries of IGEs and GGEs, or what is accepted within a clinical spectrum of a definite IGE. Here, we discuss several entities that have been described in the literature for many years and that may either constitute rare features of IGEs or a distinct differential diagnosis. Their recognition by clinicians may allow a more individualized approach and improve the management of patients presenting with such entities.

A decade of fingolimod in multiple sclerosis: Insights from a large real-world cohort study.

BACKGROUND AND OBJECTIVES: Ten years after its authorization, data about fingolimod use in real-world setting is still scarce. Here we describe the long-term evolution of fingolimod-treated relapsing-remitting MS (RRMS) patients and determine baseline characteristics associated with risk of relapses or disability. METHODS: We analyzed baseline characteristics and clinical evolution of 1227 patients with RRMS treated with fingolimod from 2010 to 2019 in 4 French MS referral centers. We used Cox models to determine risks factors of relapses and sustained EDSS worsening. RESULTS: Median follow-up duration was 50 months, and 63% of patients remained fingolimod-treated at the end of follow-up. Mean 5-years annualized relapse rate (ARR) decreased from 0.63 (0.60-0.67) to 0.26 (0.24-0.29, P<0.001), while the mean EDSS rose from 2.5 (2.4-2.6) to 3.0 (2.8-3.1, P<0.001). Female sex, lower age, higher EDSS and use of natalizumab were associated with relapse risk. Female sex was associated with sustained EDSS increase risk. CONCLUSIONS: Based on a large real-world cohort, our results confirm the durable reduction of the ARR described in pivot studies. Switching from moderate-efficacy DMT to fingolimod decreased the relapse risk. Switching patients from high-efficacy DMT increased risk of relapse, but the overall five-years ARR remained stable.

Double-blind placebo-controlled trial of adjunctive levetiracetam in pediatric partial seizures.

OBJECTIVE: To evaluate the efficacy and tolerability of levetiracetam (LEV) as adjunctive therapy in children (4 to 16 years) with treatment-resistant partial-onset seizures. METHODS: This multicenter, randomized, placebo-controlled trial consisted of an 8-week baseline period followed by a 14-week double-blind treatment period. During the treatment period, patients received either placebo or LEV add-on therapy and were up-titrated to a target dose of 60 mg/kg/day. RESULTS: One hundred ninety-eight patients (intent-to-treat population) provided evaluable data. The reduction in partial-onset seizure frequency per week for LEV adjunctive therapy over placebo adjunctive therapy was significant (26.8%; p = 0.0002; 95% CI 14.0% to 37.6%). A 50% or greater reduction of partial seizure frequency per week was attained in 44.6% of the LEV group (45/101 patients), compared with 19.6% (19/97 patients) receiving placebo (p = 0.0002). Seven (6.9%) LEV-treated patients were seizure-free during the entire double-blind treatment period, compared with one (1.0%) placebo-treated patient. One or more adverse events were reported by 88.1% of LEV-treated patients and 91.8% of placebo patients. The most common treatment-emergent adverse events were somnolence, accidental injury, vomiting, anorexia, hostility, nervousness, rhinitis, cough, and pharyngitis. A similar number of patients in each group required a dose reduction or withdrew from the study as a result of an adverse event. CONCLUSION: Levetiracetam adjunctive therapy administered at 60 mg/kg/day is efficacious and well tolerated in children with treatment-resistant partial seizures.

Genetic variation in natural populations of maté (Ilex paraguariensis A. st.-hil., aquifoliaceae) using RAPD markers.

This study characterized the genetic diversity of four populations of Ilex paraguariensis, a plant species native to South America, using random amplified polymorphic DNA (RAPD) markers. A total of 341 different RAPD bands were generated by the 15 primers analysed. High genetic variability was detected within each population, with an average diversity of 0.163. The within-population variation was large, probably as a result of the life history characteristics of I. paraguariensis. The average distance between individuals from each population was 0.392 and that between populations was 0.433, indicating a low between-population divergence. Most bands were common to all populations and the population-specific bands occurred at low frequencies. Partitioning of the genetic diversity indicated that 85% of the variation occurred within populations and only 15% between populations. Although most of the variability is within populations, clusterings of plants in each population were observed in the dendrogram.

Effect of levetiracetam on epilepsy-related quality of life. N132 Study Group.

PURPOSE: To evaluate the short-term effect of levetiracetam (LEV; UCB L059) as add-on therapy on health-related quality of life in the treatment of refractory partial-onset seizures. METHODS: Patients were enrolled in protocol UCB N132 if they had >/=12 partial-onset seizures with or without secondary generalization during the 12-week baseline period with a minimum of two seizures every 4 weeks. Randomization was made to placebo, LEV 1,000 mg, or LEV 3,000 mg, with sample size based on seizure frequency reduction. The 31-item Quality of Life in Epilepsy (QOLIE-31) questionnaire was completed by 246 patients at the end of baseline and at 18-week follow-up, or earlier if withdrawn. RESULTS: Significant differences were found among the three treatment groups for Seizure Worry (p = 0. 0003), Overall Quality of Life (p = 0.04), and Cognitive Functioning domains (p = 0.01), as well as the Total Score (p = 0.009). Responders (>/=50% partial onset seizure reduction) had significant improvements in all areas, except Medication Effect, compared with nonresponders (all p > 0.006). Clinically noticeable improvement (>/=10% change from baseline to follow-up) was perceived by LEV 3, 000 mg responders in all areas, except Emotional Well-Being, by LEV 1,000 mg responders in 5 of 9 areas, and by placebo responders in 2 of 9 areas. CONCLUSIONS: Addition of LEV to standard medication seems to have a positive impact on health-related quality of life, particularly among responders in this short-term study. These exploratory analyses require additional studies to evaluate long-term changes in a larger population.

Levetiracetam for partial seizures: results of a double-blind, randomized clinical trial.

OBJECTIVE: To evaluate the efficacy and safety of 500 mg bid and 1500 mg bid levetiracetam as adjunctive therapy for refractory partial seizures in a double-blind, randomized, placebo-controlled, parallel-group, multicenter trial. METHODS: The authors studied patients with uncontrolled partial seizures (minimum 12 per 12 weeks), regardless of whether they became secondarily generalized, for 38 weeks. A 12-week baseline was followed by random assignment to adjunctive therapy with placebo (n = 95), levetiracetam 1000 mg/day (n = 98), or levetiracetam 3000 mg/day (n = 101). Upward titration over 4 weeks was followed by 14 weeks of fixed dose treatment, and concluded with an 8-week medication withdrawal period or entering a follow-up study. RESULTS: Of 294 patients randomized, 268 completed the study. Partial seizure frequency during the entire evaluation period (primary efficacy variable) was lower with levetiracetam compared to placebo (p /=10%), mostly mild to moderate in severity, with incidences higher than placebo were asthenia, dizziness, flu syndrome, headache, infection, rhinitis, and somnolence. CONCLUSION: Adjunctive therapy with levetiracetam was effective and well tolerated in controlling partial seizures.