Search

• Post hoc analyses of patients with temporal lobe epilepsy (TLE). • Patients on lacosamide (LCM) or controlled-release carbamazepine (CBZ-CR) monotherapy. • Stratified Kaplan–Meier estimates for seizure freedom were similar for LCM and CBZ-CR. • TEAEs were reported by numerically fewer patients on LCM (73.9%) than CBZ-CR (81.0%). • LCM was efficacious and generally well tolerated as monotherapy in patients with TLE. Temporal lobe epilepsy (TLE) is often associated with drug-resistant seizures. We evaluated the efficacy and tolerability of lacosamide (LCM) versus controlled-release carbamazepine (CBZ-CR) monotherapy in adults with newly diagnosed TLE. Exploratory post hoc analysis of patients with temporal focus of localization (indicated as the only localization focus) in a double-blind, noninferiority, phase 3 trial (SP0993; NCT01243177) in patients aged ≥ 16 years with newly diagnosed epilepsy randomized 1:1 to LCM or CBZ-CR monotherapy. Of 886 treated patients in this trial, temporal lobe focus of localization (TLE) was reported as the single focus for 287 (32.4%) patients (LCM 134, CBZ-CR 153). A similar proportion of patients with TLE on LCM (82 [61.2%]) and CBZ-CR (99 [64.7%]) completed the trial. Kaplan-Meier estimates for 6- and 12-month seizure freedom at the last evaluated dose level (stratified by number of seizures in the 3 months before screening [≤2 or >2 seizures]) were similar with LCM and CBZ-CR (6 months overall: 88.7% and 89.7%; 12 months overall: 78.3% and 81.7%). Treatment-emergent adverse events (TEAEs) were reported by fewer patients on LCM (73.9%) than CBZ-CR (81.0%). Drug-related TEAEs (assessed by the investigator) were reported in 41.8% of patients on LCM and 52.3% of patients on CBZ-CR; 11.2% of patients on LCM and 15.0% on CBZ-CR discontinued due to TEAEs. Lacosamide was efficacious and generally well tolerated as monotherapy in patients with TLE with efficacy outcomes comparable with CBZ-CR, and fewer patients on LCM reported any TEAEs, drug-related TEAEs, or discontinued due to TEAEs. [ABSTRACT FROM AUTHOR]

• HRV-based seizure detection achieves good detection sensitivity of focal seizures. • Patient adaptive seizure detection threshold outperformed generic threshold. • The proposed machine learning method reduced FAR by 31% compared to previous methods. Wearable automated detection devices of focal epileptic seizures are needed to alert patients and caregivers and to optimize the medical treatment. Heart rate variability (HRV)-based seizure detection devices have presented good detection sensitivity. However, false alarm rates (FAR) are too high. In this phase-2 study we pursued to decrease the FAR, by using patient-adaptive logistic regression machine learning (LRML) to improve the performance of a previously published HRV-based seizure detection algorithm. ECG-data were prospectively collected using a dedicated wearable electrocardiogram-device during long-term video-EEG monitoring. Sixty-two patients had 174 seizures during 4,614 h recording. The dataset was divided into training-, cross-validation-, and test-sets (chronological) in order to avoid overfitting. Patients with >50 beats/min change in heart rate during first recorded seizure were selected as responders. We compared 18 LRML-settings to find the optimal algorithm. The patient-adaptive LRML-classifier in combination with using only responders to train the initial decision boundary was superior to both the generic approach and including non-responders to train the LRML-classifier. Using the optimal setting of the LRML in responders in the test dataset yielded a sensitivity of 78.2% and FAR of 0.62/24 h. The FAR was reduced by 31% compared to the previous method, upholding similar sensitivity. The novel, patient-adaptive LRML seizure detection algorithm outperformed both the generic approach and the previously published patient-tailored method. The proposed method can be implemented in a wearable online HRV-based seizure detection system alerting patients and caregivers of seizures and improve seizure-count which may help optimizing the patient treatment. [ABSTRACT FROM AUTHOR]

Objective: Post-stroke epilepsy (PSE) is one of the most common causes of acquired epilepsy and accounts for about 10-15% of all newly diagnosed epilepsy cases. However, evidence about the clinical profile of antiseizure medications in the PSE setting is currently limited. Brivaracetam (BRV) is a rationally developed compound characterized by high-affinity binding to synaptic vesicle protein 2A. The aim of this study was to assess the 12-month effectiveness and tolerability of adjunctive BRV in patients with PSE treated in a real-world setting.Methods: This was a subgroup analysis of patients with PSE included in the BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST). The BRIVAFIRST was a 12-month retrospective, multicentre study including adult patients prescribed adjunctive BRV. Effectiveness outcomes included the rates of seizure response (≥50% reduction in baseline seizure frequency), seizure-freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events (AEs) and the incidence of AEs.Results: Patients with PSE included in the BRIVAFIRST were 75 and had a median age of 57 (interquartile range, 42-66) years. The median daily doses of BRV at 3, 6, and 12 months from starting treatment were 100 (100-150) mg, 125 (100-200) mg and 100 (100-200) mg, respectively. At 12 months, 32 (42.7%) patients had a reduction in their baseline seizure frequency by at least 50%, and the seizure freedom rates was 26/75 (34.7%). During the 1-year study period, 10 (13.3%) patients discontinued BRV. The reasons of treatment withdrawal were insufficient efficacy in 6 (8.0%) patients and poor tolerability in 4 (5.3%) patients. Adverse events were reported by 13 (20.3%) patients and were rated as mild in 84.6% and moderate in 15.4% of cases.Significance: Adjunctive BRV was efficacious and generally well-tolerated when used in patients with PSE in clinical practice. Adjunctive BRV can be a suitable therapeutic option for patients with PSE. [ABSTRACT FROM AUTHOR]

Purpose: To assess how efficacy and safety outcomes were affected when cenobamate was co-administered with antiseizure medications (ASMs) that use either sodium channel blocker (SCB) or non-sodium channel blocker (non-SCB) mechanisms of action (MoAs) in patients with uncontrolled focal seizures.Methods: An exploratory post-hoc analysis of a randomized, double-blind, placebo-controlled clinical study (YKP3089C017) was conducted. Baseline concomitant ASMs were grouped as either those that employed an SCB or non-SCB MoA. Efficacy was examined by cenobamate dose (100 mg, 200 mg, and 400 mg/day) and concomitant ASM group using responder rates (≥50%, ≥75%, ≥90% seizure reduction; 100% seizure reduction/seizure freedom) during the maintenance phase and median percentage seizure reduction during the double-blind period. Treatment-emergent adverse events (TEAEs) were examined in the double-blind period.Results: When co-administered with SCBs or non-SCBs, significantly higher percentages of patients achieved ≥50%, ≥75%, and ≥90% responder rates with cenobamate 200 mg/day and/or 400 mg/day versus placebo. Additionally, significantly higher percentages of patients achieved seizure freedom with cenobamate 400 mg/day versus placebo (SCB group, 17.5% versus 1.2%; non-SCB group, 40.0% versus 0.0%). Patients receiving 200 mg/day and 400 mg/day and concomitant SCBs and all patients taking cenobamate combined with non-SCB concomitant ASMs had significantly greater median percentage reductions in focal seizure frequency versus placebo. TEAEs were similar across groups; however, dizziness was more frequently reported in the SCB group.Conclusion: Cenobamate is a highly effective new treatment option for patients with uncontrolled focal seizures when co-administered with SCB or non-SCB ASMs. [ABSTRACT FROM AUTHOR]

Objectives: To identify semiologic features of automatisms correlating to different seizure onset zones (SOZ).Methods: In total, 204 seizures from 74 patients with either oral or manual automatisms were assessed. Patients were divided into four groups depending on the SOZ into frontal, posterior, neocortical temporal, and mesial temporal cortex groups. A k-means analysis was applied on 11 semiologic features on a multi-criteria scale. Then, the resulting clinical patterns were correlated with the SOZs determined by presurgical anatomy-electroclinical data (25 cases with stereo-EEG).Results: Four clinical patterns of automatisms with different accompanying symptoms were identified. The clinical features of clusters 1 and 4 were mostly found in temporal epilepsy whereas clusters 2 and 3 were more frequent in extratemporal epilepsy. Cluster 1 was significantly correlated with mesial temporal lobe epilepsy (p = .017) and was characterised by aura, postictal confusion, short automatisms delay. Cluster 3 included 1/3 patients with frontal lobe epilepsy and was characterised by emotionality. Cluster 4 was related to neocortical temporal lobe epilepsy and characterised by dystonia and short automatism delay (p = .011).Conclusion: The distinct semiologic patterns of automatisms may provide information which may allow clinicians to define the SOZs. These findings could improve diagnostic accuracy and surgical outcome. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose We present six patients with epilepsy of infancy with migrating focal seizures (EIMFS) and provide a comprehensive evaluation of potassium bromide therapy. Method Between February 1, 2007 and July 31, 2012, six patients who met the diagnostic criteria of EIMFS were treated with potassium bromide. Potassium bromide was added to other antiepileptic drugs (AEDs) in doses ranging from 30 to 80 mg/kg/day. Plasma bromide concentration was monitored. A therapeutic bromide concentration between 75 and 125 mg/dL was considered to be ideal. Results Four of six children responded well to bromide. One of these patients became seizure free, but remained severely mentally impaired. Two boys, currently 4 and 6 years of age, respectively, have monthly seizures as well as axial hypotonia and severe language impairment. The fourth child responded well to bromide, having only weekly seizures and moderate psychomotor retardation. The patient who became seizure free improved visual contact and head control. In the other three patients with good control, the seizures became focal without secondary generalization and status epilepticus and hospital admission was not required. The remaining two patients did not respond well to bromide. Adverse effects were seen in three cases: vomiting in one, drowsiness in another, and acneiform eruption in the face in the remaining patient. Adverse effects resolved with dose reduction. Conclusion Early treatment with bromides should be considered in EIMFS to control the seizures and status epilepticus and to avoid progressive cognitive impairment. Potassium bromide is an old AED. Plasma concentration monitoring should be considered. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Dravet syndrome (DS) is a rare disorder with seizure onset in the first year of life, typically beginning with prolonged febrile hemiclonic seizures or generalized tonic–clonic seizures. Photosensitivity is reported in more than 40% of patients. We present two cases of DS in which we had the chance to record occipital seizures induced by Intermittent Photic Stimulation (IPS). Method: We retrospectively reviewed the medical records of 32 children affected by DS. All clinical notes were reviewed in order to evaluate the occurrence of seizures induced by IPS. Results: Among the 32 reviewed clinical records, two patients with IPS-induced seizures were found. In both patients seizures originated from the occipital-temporal region. Clinical history was characterized by generalized tonic–clonic seizures, and myoclonia. At the age respectively of 11 months and 20 months they presented a prolonged focal seizure induced by IPS at a frequency of 10Hz. During the follow-up they additionally presented with hypomotor seizures, also induced by IPS during laboratory EEG examinations. The semiology of hypomotor seizures resembled what is described as “complex partial status”, a type of non-convulsive status with ictal discharges arising unilaterally from the occipito-temporal region. Conclusion: Based on available literature, IPS induced occipital seizures have not been reported during the first year of life. Although pathophysiological features are not yet completely understood, both photosensitivity and occipital seizures should be considered in the diagnostic evaluation in DS. The documentation of IPS induced occipital seizures might contribute to widen the clinical and neurophysiological spectra of DS. [Copyright &y& Elsevier]

Abstract: Circadian rhythm of seizure is underestimated in the study of focal epilepsies. A review of the current literature revealed a clear correlation between cortical epileptogenic focus and the circadian phase of seizure peak occurrence in adult patients. A single diurnal peak at 19:00 was found in seizures originating from the occipital lobe, between 5:00 and 7:00 in frontal lobe seizures, and between 16:00 and 17:00h in temporal lobe seizures. Two diurnal peaks, between 5:00 and 7:00, and at 23:00 are reported in seizures from the parietal lobe, and between 7:00 to 8:00 and 16:00 to 17:00 in mesial temporal onset seizures. This circadian character of seizure occurrence in focal epilepsies may not be unique to partial seizures since recent clinical and experimental data indicate that generalized seizures also demonstrate circadian effects. The clinical evidence on generalized seizures and epilepsies is not recent, but a formal integration of circadian rhythmicity in our understanding and clinical management of epilepsies may be warranted. [Copyright &y& Elsevier]