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Purpose Perampanel (PER) and lacosamide (LCM) are antiepileptic drugs (AEDs) approved for the adjunctive treatment of partial-onset seizures. At the time of market entry, information on clinical effectiveness of new AEDs is limited to results from pivotal trials, real-life or comparative data are missing. This analysis of data collected retrospectively in a German epilepsy center used unified evaluation criteria, and describes treatment outcomes with LCM and PER at 6 months. Methods Results of the first 70 consecutive patients who had received LCM or PER after their market entries in Germany were compared. Outcome measures comprised 50% responder rates, seizure freedom, retention, and incidence of adverse events (AEs). Results The mean number of previous AEDs was 8.7 in the PER group, and 7.3 in the LCM group. At 6 months, the 50% responder rate for all seizures was 48.6% for PER, and 28.6% for LCM, with seizure freedom in 14.3% of patients with PER, and 4.3% with LCM. Thirty-two AEs were reported for LCM, and 51 for PER, most commonly dizziness (22.9% of patients) for LCM, and somnolence/tiredness for PER (41.4%). AEs were reported as primary reason for discontinuation in 3 patients of the PER group. Retention rates were similar. Conclusions This analysis describes initial comparative benefits of two newly available AEDs in two cohorts of patients with highly refractory epilepsies. Responder and seizure freedom rates were numerically higher for PER. The analysis suggests that new AEDs can provide a chance for seizure freedom in relevant subgroups of patients, despite previous failure of multiple AEDs.

Hintergrund Unter antikonvulsiver Monotherapie erreichen Patienten mit fokaler Epilepsie oft keine befriedigende Anfallskontrolle bzw. zeigen deutliche Nebenwirkungen bei hohen Dosierungen. Kombinationen von Antikonvulsiva sind in diesen Konstellationen haufig das Mittel der Wahl. Eslicarbazepinacetat (ESL) ist als Zusatztherapie zur Behandlung fokaler Anfalle zugelassen und besitzt ein gunstiges Vertraglichkeitsprofil.

Eslicarbazepinacetat (ESL) ist ein Antikonvulsivum, das zur Zusatztherapie bei Erwachsenen mit fokalen epileptischen Anfallen zugelassen ist. Analyse von Einsatz, Wirksamkeit und Vertraglichkeit von ESL in der klinischen Behandlungspraxis in Deutschland. Retrospektive Datensammlung in 18 neurologischen Zentren von Patienten mit fokaler Epilepsie, die ab 1. Januar 2012 konsekutiv auf eine Begleittherapie mit ESL eingestellt wurden. In einem standardisierten elektronischen Dokumentationsbogen wurden Daten zum Einsatz sowie zu Wirksamkeit und Vertraglichkeit von ESL erfasst. 125 Patienten (medianes Alter: 48 Jahre (Spanne 20–83 Jahre), 59,2 % mannlich) wurden in die Analyse eingeschlossen. Bessere Anfallskontrolle (70,4 % der Patienten) und bessere Vertraglichkeit (20,8 %) stellten die am haufigsten genannten Primarziele der Behandlung mit ESL dar. Erste ESL-Zieldosis und letzte Behandlungsdosis betrugen im Median jeweils 800 mg (Spanne 400–2400 mg). Die Responderrate, definiert als Patientenanteil mit Anfallsreduktion gegenuber Baseline um ≥50 %, betrug nach 3, 6 und 12 Monaten 46,7 %, 53,3 % und 55,3 %. Bei der letzten dokumentierten Visite waren 38,8 % der Patienten fur ≥3 Monate anfallsfrei. Der Zeitraum zwischen Einstellung und letzter dokumentierter Visite betrug im Durchschnitt 397 ± 246 Tage. Die Wirksamkeit von ESL wurde vom Arzt bei 61,6 % der Patienten und die Vertraglichkeit bei 70,4 % der Patienten mit sehr gut oder gut beurteilt. 12,0 % der Patienten brachen die Therapie aufgrund von unerwunschten Ereignissen (UE) ab. Haufiger (≥5 %) berichtete UE waren Fatigue, Schwindel und Hyponatriamie. Insgesamt verblieben 77 % der Patienten fur ≥12 Monate auf Therapie mit ESL. Die antikonvulsive Begleittherapie mit ESL stellte sich in der vorliegenden Sammlung aktueller Praxisdaten in Deutschland als gut wirksam und vertraglich dar.

Eslicarbazepine acetate (ESL) is a third-generation antiepileptic drug (AED) approved as monotherapy for partial-onset seizures in adults and as adjunctive therapy in patients aged above 6 years in the European Union (EU). The prospective observational Zebinix Effects in DEpendency of BAseline Conditions (ZEDEBAC) study aimed at investigating the effectiveness of ESL in clinical practice, with ESL being administered as monotherapy (mono group), as only add-on to a current monotherapy (1 + group), or as add-on to ≥ 2 baseline AEDs (≥ 2 + group). In total, 237 patients were included, 35 in the mono group, 114 in the 1 +, and 88 in the ≥ 2 + group. Six-month retention rates were 93.9%, 78.0%, and 75.3% in the mono, 1 +, and ≥ 2 + group. There were 90.5%, 77.6%, and 48.3% of patients in the mono, 1 +, and ≥ 2 + groups who were responders (patients with a ≥ 50% reduction in seizure frequency at follow-up vs. baseline). Seizure freedom rates were 81.5%, 47.9%, and 23.4%, respectively. Adverse drug reactions (ADRs) occurred in 11.4% of patients of the mono, 19.3% of the 1 +, and 28.4% of patients of the ≥ 2 + group. Hyponatremia was reported as ADR in 3.4% of all patients. Although baseline variables differed considerably, with most elderly patients with tumor-related and vascular etiologies in the mono group and most patients with refractory epilepsies with pronounced use of concomitant sodium channel blockers (SCBs) in the ≥ 2 + group, retention as a measure of real-life effectiveness turned out not to be substantially different and favorable in all groups.

Objective To assess retention, tolerability, and safety, efficacy and effects on quality of life (QoL) of eslicarbazepine acetate (ESL) add‐on treatment over 6 months in a real‐world adult population with partial‐onset seizures. Methods This non‐interventional, multicenter, prospective study was performed in eight European countries. Adult patients (n = 247) for whom the physician had decided to initiate ESL as add‐on to an existing antiepileptic drug (AED) monotherapy were invited to participate. The study comprised three visits: baseline, and after 3 and 6 months. Data on ESL retention, efficacy, tolerability, safety, and QoL were collected. Results After 6 months, the retention rate of ESL was 82.2%, and 81.8% of patients reported a reduction of seizure frequency of at least 50%; 39.2% of patients reported seizure freedom at this time. The mean QOLIE‐10 score improved from 2.9 (SD ± 0.8) at baseline to 2.1 (SD ± 0.8) after 6 months. 109 adverse events (AEs) were reported in 57 patients (26.0%); the majority were rated as related to ESL by the investigator and led to a discontinuation of ESL in 25 patients (11.4%). Eight patients (3.7%) suffered at least one serious AE. The most frequently reported AEs were dizziness, headache, convulsion, and fatigue. Conclusions This study shows that ESL was well tolerated and efficacious as add‐on therapy to one baseline AED. The use of ESL in patients less refractory than those included in previous clinical trials led to higher responder and seizure freedom rates. No new safety issues were observed.

Objectives The goals of this study were to observe behavioral changes in patients receiving levetiracetam (LEV), a newer antiepileptic drug (AED), and to answer the question of whether LEV exerts a specific effect on impulse control and aggression. Methods We asked 288 consecutive patients with epilepsy on LEV (90% polytherapy, mean dose = 2689 mg) and 135 relatives whether LEV caused a positive or negative behavioral change. Forty-three patients on other AEDs served as a control group. Ratings were related to patient characteristics, efficacy, dose, drug load, bidirectional ratings of change in behavioral domains, and questionnaires on personality (Fragebogens zur Personlichkeit bei zerebralen Erkrankungen) and impulsivity (Barratt Impulsiveness Scale-11). Results LEV was rated as very effective by 40% of the patients. In contrast to only 9% of the controls, a considerable number of patients reported a behavioral change while taking LEV (12% very negative, 25% negative, 16% positive, 6% very positive). Negative ratings were due to loss of self-control, restlessness, sleep problems, and, most importantly, aggression. Positive ratings were due to increased energy, vigilance, and activation. Increases in psychomotor speed, concentration, and remote memory indicated subjectively experienced positive effects on cognition. The proxy reports indicated reliable self-reports. Reported change was not related to type of epilepsy, co-therapy, dose, drug load, or psychiatric history. Negative effects were, however, associated with poorer seizure control, mental retardation, indicators of an organic psychosyndrome, and nonplanning impulsiveness. Conclusion The results indicate that LEV exerts a dose-independent stimulating effect that can be positive or negative. Aggression is a prominent feature. Lack of efficacy, mental retardation, and presumably also pre-intake disposition (organic psychosyndrome, impulsivity) may be helpful in predicting whether additional activation under LEV will be positive or negative.

We compared surface and intracranial electroencephalogram recordings of mediotemporal structures. These structures are critically involved in declarative memory formation and memory consolidation during sleep. As memory processing is suggested to involve the interplay between fast and slow oscillations, we hypothesized different correlations between frequency bands in surface versus mediotemporal electroencephalogram recordings. Polysomnographic recordings obtained in 10 patients with unilateral temporal lobe epilepsy were analyzed. In accordance with earlier studies, we observed that power density in surface electroencephalogram is organized reciprocally between delta/theta and fast frequencies above 16 Hz during non-rapid-eye-movement sleep (negative correlations). In contrast, we found that within the hippocampus delta/theta power alternated in parallel with fast oscillations above 16 Hz during non-rapid-eye-movement sleep (positive correlations).

Purpose Zonisamide is licensed for adjunctive therapy for partial-onset seizures with or without secondary generalisation in patients 6 years and older and as monotherapy for the treatment of partial seizures in adult patients with newly diagnosed epilepsy, and shows a favourable pharmacokinetic profile with low interaction potential with other drugs. The aim of the present study was to gather real-life data on retention and modalities of zonisamide use when administered as only add-on treatment to a current AED monotherapy in adult patients with partial-onset seizures. Methods This multicenter observational study was performed in 4 European countries and comprised three visits: baseline, and after 3 and 6 months. Data on patients' retention, reported efficacy, tolerability and safety, and quality of life was collected. Of 100 included patients, 93 could be evaluated. Results After 6 months, the retention rate of zonisamide add-on therapy was 82.8%. At this time, a reduction of seizure frequency of at least 50% was observed in 79.7% of patients, with 43.6% reporting seizure freedom over the last 3 months of the study period. Adverse events were reported by 19.4% of patients, with fatigue, agitation, dizziness, and headache being most frequent. Approximately 25% of patients were older than 60 years, many of whom suffered from late-onset epilepsy. Compared to younger patients, these patients showed considerable differences with regard to their antiepileptic drug regimen at baseline, and slightly higher responder and retention rates at 6 months. Conclusions Despite limitations due to the non-interventional open-label design and the low sample size, the results show that zonisamide as only add-on therapy is well retained, indicating effectiveness in the majority of patients under real-life conditions.

Rationale This retrospective study was conducted to identify cognitive domains affected by topiramate (TPM), and to evaluate the role of blood serum levels of TPM and comedication in the etiology of TPM-induced cognitive impairment. Methods Forty-two patients on AED polytherapy containing topiramate and a random sample of 42 patients with lamotrigine as the corresponding agent underwent extensive neuropsychological testing. Current blood serum levels of TPM were correlated with test scores. Results Patients on TPM scored significantly worse in phonematic verbal fluency, memory spans, and working memory; language and memory function were not affected per se. In few cognitive domains, serum levels of TPM and performance were correlated before correction for multiple testing. Drug load of additional medication did not account for differences between or within groups. Discussion Consistent with previous reports, patients on AED polytherapy including TPM display a cognitive pattern with specific impairment in executive functions. The severity of the cognitive side effects of TPM may be related to dosing to a certain extent, but this relationship may be disclosed only with larger sample sizes. Accordingly, TPM dosage does not appear to be a good indicator of TPM-related cognitive side effects in the individual patient.

Purpose To assess retention rate, seizure control and safety/tolerability of eslicarbazepine acetate (ESL) as add-on to antiepileptic monotherapy in everyday clinical practice across eight European countries. Method Eslicarbazepine acetate in Partial-Onset Seizures (EPOS) was a prospective, non-interventional study conducted in adult patients with uncontrolled partial-onset seizures under antiepileptic monotherapy, whose clinician had previously and independently decided to initiate ESL add-on therapy. Primary endpoint was retention rate after 6 months. Other assessments included responder and seizure freedom rates after 6 months, and safety/tolerability. Results Overall, 219 patients were included (mean age 45.9 years; 57.5% male). Mean time since epilepsy diagnosis was 12.3 years. Mean ESL dose after titration was 944.8 mg/day (range 428.6–2800.0 mg/day). After 6 months, retention, responder and seizure freedom rates were 82.2% (95% confidence interval [CI] 76.5–87.0%), 81.8% (95% CI 75.5–87.1%) and 39.2% (95% CI 32.2–46.5%), respectively. Adverse events (AEs) were reported for 57 (26.0%) patients (most commonly dizziness [4.6%]); eight (3.7%) patients experienced serious AEs. No AE was reported in >5% of patients. Conclusion ESL as add-on to antiepileptic monotherapy demonstrated favourable retention and seizure control, and was well tolerated by the majority of adult patients in a real-life setting. Supported by Eisai.

Cognitive impairment is frequent in temporal lobe epilepsy (TLE). In particular, specific deficits in temporal lobe related functions occur, but deficits in extratemporal lobe functions and global intelligence are also found. The degree and type of the impairment are first determined by structural damage and functionally dynamic factors. Most cognitive problems in TLE are already detectable at, or even before, the onset of the epilepsy. Accumulation of damage during the course of chronic epilepsy may add to this. This additional damage may be caused directly by severe seizures, head trauma, intoxication etc., or indirectly by interference of the epilepsy with mental development. Surgical treatment of TLE may also affect the cognitive outcome of patients with chronic TLE, with a risk of additional impairments on the one hand and functional recovery due to seizure control on the other hand. With regard to patient-associated factors, better baseline performance, younger age, cerebral plasticity, and good mental reserve capacities are associated with a better outcome. With regard to treatment-associated factors, prevention of additional brain dysfunction/damage and successful seizure control are important.

Contains fulltext : 50340.pdf (Publisher’s version ) (Closed access) Compared with waking state attention, volition and semantic processing play a minor role during sleep. Thus, investigating declarative memory formation during sleep may allow us to isolate mnemonic core processes. The most feasible approach to memory formation during sleep is the analysis of dream memories. Lesion and imaging studies have demonstrated that encoding of declarative memories, i.e. consciously accessible events and facts, depends on operations within the rhinal cortex and the hippocampus, two substructures of the medial temporal lobe. Successful memory formation is accompanied by a transient rhinal-hippocampal interaction. Consequently, the ability to memorize dreams may be related to mediotemporal connectivity. Therefore, we recorded EEG during sleep from rhinal and hippocampal depth electrodes implanted in 12 epilepsy patients (eight women, mean age 41.1 +/- 6.4 years). They were awakened during rapid eye movement sleep (REM) and asked to recall their dream. Via coherence analyses we show that rhinal-hippocampal connectivity values are approximately twice as large for patients with good dream recall versus those patients with poor recall. This suggests that rhinal-hippocampal connectivity is a key factor in determining declarative memory formation.

Rationale : Topiramate (TPM) is a highly effective anticonvulsant drug, but a comparably high rate of cognitive adverse effects have been reported. In this study, we investigated changes in frontal lobe associated cognitive measures after TPM withdrawal in epilepsy patients hospitalized for presurgical evaluation. Methods : Twenty epilepsy patients were administered a brief neuropsychological test battery before and after withdrawal of TPM. Neuropsychological evaluation included a verbal fluency task, verbal (Wechsler's digits) and spatial spans (Corsi block-tapping) and Trail Making Test (TMT, parts A and B). Median baseline dosage of TPM was 237.5mg/d, the median retest-interval was 8 days. Results were compared to a matched group of patients, who had been tested and retested before and after reduction of AEDs other than TPM at comparable time intervals. Results : After TPM withdrawal, group performance appeared significantly improved in five of six tests administered. The scores of the control patients remained largely unchanged after drug reduction. After withdrawal, the scores of the TPM group did not differ significantly from the results of the control group whereas pronounced differences had been observed before. Individual improvement became apparent in the majority of patients. Cognitive performance was not correlated to current daily dosages/current blood serum levels of TPM. Conclusion : Withdrawal of TPM causes significant improvement in frontal lobe associated measures like verbal fluency and working memory. As withdrawal was part of the preoperative work-up, and not initiated because of patients' complaints or hints of intoxication, cognitive impairment due to TPM appears to be easily overlooked and underestimated.

Item does not contain fulltext The deficiency of declarative memory compared with waking state is an often overlooked characteristic of sleep. Here, we investigated whether rhinal-hippocampal coherence, an electrophysiological correlate of declarative memory formation, is significantly altered during sleep as compared with waking state. For this purpose, we analysed recordings of intracranial EEG activity during sleep obtained directly from within the medial temporal lobe in patients with unilateral temporal lobe epilepsy. We found a general reduction of rhinal-hippocampal EEG coherence during sleep compared with waking state, which was most pronounced within the upper gamma bands (average decrease up to 56%). The observed coherence changes clearly differ from findings reported for surface EEG data and thus appear to be specific for the medial temporal lobe. The decrease of rhinal-hippocampal EEG coherence from waking state towards sleep may yield an electrophysiological explanation for the sleep-related deficiency of declarative memory.