Verbal Learning and Longitudinal Hippocampal Network Connectivity in Temporal Lobe Epilepsy Surgery

IntroductionLearning new verbal information can be impaired in 20-40% of patients after mesial temporal lobe resection. In recent years, understanding epilepsy as a brain network disease, and investigating the relationship between large-scale resting networks and cognition has led to several advances. Aligned studies suggest that it is the integrity of the hippocampal connectivity with these large-scale networks what is relevant for cognition, with evidence showing a functional and structural heterogeneity along the long axis hippocampus bilaterally. ObjectiveOur aim is to examine whether pre-operative resting-state connectivity along the long hippocampal axis is associated with verbal learning decline after anterior temporal lobe resection. MethodsThirty-one patients with epilepsy who underwent an anterior temporal lobe resection were pre-surgically scanned at 3-tesla, and pre/post-surgery evaluated for learning deficits using the Rey Auditory Verbal Learning Task (RAVLT). Eighteen controls matched by age, gender and handedness were also scanned and evaluated with the RAVLT. We studied the functional connectivity along the (anterior/posterior) long axis hippocampal subregions and resting-state functionally-defined brain networks involved in learning [executive (EXE), dorsal attention (DAN) and default-mode (DMN) networks]. Functional connectivity differences between the two groups of patients (learning intact or with learning decline) and controls were investigated with MANOVA and discriminant analysis. ResultsThere were significant differences in the pattern of hippocampal connectivity among the groups. Regarding the anterior connectivity hippocampal pattern, our data showed an increase of connectivity in the pathological side with the DAN (p = 0.011) and the EXE (p = 0.008) when comparing learning-decline vs. learning-intact patients. Moreover, the non-pathological side showed an increase in the anterior connectivity pattern with the DAN (p = 0.027) between learning-decline vs. learning-intact patients. In contrast, the posterior hippocampus showed a reduction of connectivity in the learning-decline patients with the DMN, both in the pathological (p = 0.004) and the non-pathological sides (p = 0.036). Finally, the discriminant analysis based on the pre-operative connectivity pattern significantly differentiated the learning-decline patients from the other groups (p = 0.019). ConclusionOur findings reveal bilateral connectivity disruptions along the longitudinal axis of the hippocampi with resting-state networks, which could be key to identify those patients at risk of verbal learning decline after epilepsy surgery

Real-Life Effectiveness and Tolerability of Brivaracetam in Focal to Bilateral and Primary Generalized Tonic-Clonic Seizures

Effectiveness; Brivaracetam; Tonic-clonic seizuresEfectividad; Brivaracetam; Convulsiones tónico-clónicasEfectivitat; Brivaracetam; Convulsions tònic-clòniquesPurpose. Brivaracetam (BRV), an antiseizure medication indicated for focal-onset seizures, has shown efficacy in the treatment of focal to bilateral tonic-clonic seizures (FBTCS). We aimed to determine the effectiveness and safety of BRV in patients with FBTCS and generalized tonic-clonic seizures (GTCS). Methods. We performed a multicenter, retrospective, longitudinal study in adult patients with epilepsy who experienced at least one FBTCS or GTCS before starting BRV (baseline visit). Data were collected from consecutive outpatient visits over a 4-year period. All patients had been followed for at least 3 months before the baseline visit and completed a minimum follow-up of 3 months after starting BRV. Response (≥50% reduction in FBTCS/GTCS frequency) and retention rates, as well as seizure freedom and presence of adverse events at 3, 6, and 12 months, were recorded as outcome measures. Results. 114 patients were included (mean age years, 52% male, 36.6% genetic generalized epilepsy); 94 had a 12-month follow-up period. At 12 months’ follow-up, the response rate was 83%, and 73.4% of patients were FBTCS/GTCS-free. Retention was 79% at 12 months. Adverse events occurred in 29.8% of patients, the most common being drowsiness (14.9%). No significant differences were found in response rates between FBTCS and GTCS. Drug resistance was independently associated with lower response and seizure freedom rates at follow-up. The absence of a titration period predicted seizure freedom and response at 3 months. Conclusions. BRV is an effective and well-tolerated treatment in patients with focal to bilateral tonic-clonic seizures and generalized tonic-clonic seizures.E. Fonseca declares research funding and honoraria from UCB Pharma, Esteve Laboratorios, Eisai Inc., Bial Pharmaceutical, GW Pharmaceuticals, Angelini Pharma, and Sanofi Genzyme. A. Gifreu declares research funding from UCB Pharma and Bial Pharmaceutical. Manuel Quintana has received honoraria from UCB Pharma, Eisai Inc., Sanofi, GW Pharmaceuticals, Neuraxpharm Spain, and Pierre Fabre Ibérica. S. Lallana has received travel support and research funding from UCB Pharma and Bial Pharmaceutical. S. López-Maza declares travel support and research funding from Eisai Inc., UCB Pharma, and Neuraxpharm Spain. L. Abraira has received research funding and speaker fees from UCB Pharma, Bial Pharmaceutical, Eisai Inc., Sanofi Genzyme, and Esteve Laboratorios. D. Campos-Fernández has received research funding from UCB Pharma. E. Santamarina has received research funding and speaker fees from UCB Pharma, Bial Pharmaceutical, Eisai Inc., Arvelle, and Esteve Laboratorios. J. Rodríguez Uranga declares honoraria from Arvelle, Angelini Pharma, Bial Pharmaceutical, Eisai Inc., Esteve Laboratorios, UCB Pharma, and Pfizer Inc. M. Toledo declares research funding and speaker fees from UCB Pharma, GW Pharmaceuticals, Bial Pharmaceutical, Eisai Inc., Sanofi, Arvelle, and Esteve Laboratorios. J Abril Jaramillo and L. Redondo Vergé have no conflict of interest to declare

Risk of Developing Epilepsy after Autoimmune Encephalitis

Background: Acute symptomatic seizures (ASS) are a common manifestation of autoimmune encephalitis (AE), but the risk of developing epilepsy as a sequela of AE remains unknown, and factors predisposing the development of epilepsy have not been fully identified. Objective: To assess the risk of developing epilepsy in AE and study related risk factors. Materials and methods: This was a retrospective single centre study including patients diagnosed with AE according to criteria described by Graus et al., with a minimum follow-up of 12 months after AE resolution. The sample was divided according to whether patients developed epilepsy or not. Results: A total of 19 patients were included; 3 (15.8%) had AE with intracellular antibodies, 9 (47.4%) with extracellular antibodies, and 7 (36.8%) were seronegative. During follow-up, 3 patients (15.8%) died, 4 (21.1%) presented relapses of AE, and 11 (57.89%) developed epilepsy. There was a significant association between the development of epilepsy and the presence of hippocampal atrophy in control brain magnetic resonance imaging (MRI) (p = 0.037), interictal epileptiform discharges (IED) on control electroencephalogram (EEG) (p = 0.045), and immunotherapy delay (p = 0.016). Conclusions: Hippocampal atrophy in neuroimaging, IED on EEG during follow-up, and immunotherapy delay could be predictors of the development of epilepsy in patients with AE

Risk of Developing Epilepsy after Autoimmune Encephalitis

Background: Acute symptomatic seizures (ASS) are a common manifestation of autoimmune encephalitis (AE), but the risk of developing epilepsy as a sequela of AE remains unknown, and factors predisposing the development of epilepsy have not been fully identified. Objective: To assess the risk of developing epilepsy in AE and study related risk factors. Materials and methods: This was a retrospective single centre study including patients diagnosed with AE according to criteria described by Graus et al., with a minimum follow-up of 12 months after AE resolution. The sample was divided according to whether patients developed epilepsy or not. Results: A total of 19 patients were included; 3 (15.8%) had AE with intracellular antibodies, 9 (47.4%) with extracellular antibodies, and 7 (36.8%) were seronegative. During follow-up, 3 patients (15.8%) died, 4 (21.1%) presented relapses of AE, and 11 (57.89%) developed epilepsy. There was a significant association between the development of epilepsy and the presence of hippocampal atrophy in control brain magnetic resonance imaging (MRI) (p = 0.037), interictal epileptiform discharges (IED) on control electroencephalogram (EEG) (p = 0.045), and immunotherapy delay (p = 0.016). Conclusions: Hippocampal atrophy in neuroimaging, IED on EEG during follow-up, and immunotherapy delay could be predictors of the development of epilepsy in patients with AE