A pilot study of topiramate in childhood absence epilepsy

Piña‐Garza JE, Schwarzman L, Wiegand F, Hulihan J. A pilot study of topiramate in childhood absence epilepsy.
Acta Neurol Scand: 2011: 123: 54–59.
© 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Objective – Evaluate the antiepileptic effect of topiramate monotherapy in childhood absence epilepsy (CAE). Materials and Methods – Childhood absence epilepsy patients aged 4–9 years were initiated with topiramate 15 or 25 mg/day, which was titrated upwards until patients were free of absence seizures. The primary efficacy outcome was seizure‐free rates after a 12‐week maintenance period. Results – The study was terminated early due to lack of efficacy after enrollment of 12 patients. Four patients completed the study; two became clinically seizure‐free, but without a significant reduction in the number of electrographic seizures. Six patients discontinued for lack of efficacy, none due to adverse events (AEs). Mean reduction in seizure count was seen on Days 22 (P = 0.0391) and 36 (P = 0.0156) and percentage of days with seizures decreased from baseline. Most AEs were mild. Conclusions – Although well‐tolerated, this pilot study did not demonstrate an antiepileptic effect of topiramate monotherapy for treatment of CAE.     

Experience with topiramate monotherapy in elderly patients with recent-onset epilepsy

OBJECTIVES: To evaluate the effect of topiramate in elderly patients with onset of epilepsy after the age of 60, treatment-naive or non-responding to an initial antiepileptic drug. METHODS:Analysis of patients with epilepsy diagnosed in the preceding 5 years, aged>/=65 years (n=43), enrolled in a larger open-label trial (n=692). After titration to topiramate 100 mg/day over 4 weeks, the dose was adjusted according to individual response (maximum 400 mg/day). Patients were followed up for at least 7 months. RESULTS: After 7 months, 79% of patients remained in the study. Seizure frequency decreased significantly vs baseline (P<0.001); >/=50% reduction in seizure frequency was achieved in 87% of patients, 64% remained seizure-free. Both previously treated and naive patients responded. Fourteen per cent dropped out because of insufficient tolerability. No unexpected or unusual adverse events were observed. CONCLUSIONS: The results indicate that elderly patients respond well to topiramate monotherapy. The high patient retention rate reflects a favourable tolerability profile in this population.     

Long‐term levetiracetam treatment in patients with epilepsy: 3‐year follow up

Kuba R, Novotná I, Brázdil M, Ko?varová J, Tyrlíková I, Mastík J, Rektor I. Long‐term levetiracetam treatment in patients with epilepsy: 3‐year follow up.
Acta Neurol Scand: 2010: 121: 83–88.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives – To assess the long‐term efficacy and tolerability of levetiracetam in routine clinical practice. Materials and methods – We retrospectively analysed 218 patients, mostly adults, presenting mostly with localisation‐related epilepsy, treated with levetiracetam as adjunctive therapy or monotherapy for up to 36 months. The primary points evaluated were: long‐term retention rate, reasons for discontinuing levetiracetam and the percentage of seizure‐free patients. Results – The retention rate at 6, 12, 24 and 36 months following the commencement of levetiracetam treatment was 91.7, 75.2, 60.1 and 53.7% respectively. Sixty‐seven (30.7%) patients discontinued levetiracetam treatment. During the clinical audit evaluation period, surgical resection or implantation of VNS was performed in 31 (14.3%) patients. In 53 of the 67 patients (79.1%), the treatment was discontinued due to lack of efficacy; in 14 patients (20.9%) treatment was discontinued due to adverse events. In total, 24 of 218 patients (11.0%) were seizure‐free for 36 months. Conclusions – Levetiracetam is an effective and well‐tolerated option for long‐term treatment of epilepsy in adults.     

A comprehensive clinico‐pathological and genetic evaluation of bottom‐of‐sulcus focal cortical dysplasia in patients with difficult‐to‐localize focal epilepsy

Aims. We comprehensively studied the clinical presentation, stereo‐EEG and MRI findings, histopathological diagnosis, and brain somatic mutations in a retrospective series of drug‐resistant patients with difficult‐to‐localize epilepsy due to focal cortical dysplasia at the bottom of a sulcus (BOS‐FCD). Methods. We identified 10 patients with BOS‐FCD from the Cleveland Clinic epilepsy surgery database submitted for intracranial video‐EEG monitoring. Brain MRI, including voxel‐based morphometric analysis and surgical tissue submitted for histopathology, was reviewed. Paraffin tissue samples from five patients were made available for targeted next‐generation sequencing. Postsurgical follow‐up was available in nine patients. Results. BOS‐FCD was identified in the superior frontal sulcus in six patients, inferior frontal sulcus in one patient, central sulcus in one patient, and intraparietal sulcus in two patients. All patients had stereotyped seizures. Intracranial EEG recordings identified ictal onset at the BOS‐FCD in all 10 patients, whereas ictal scalp EEG had a localizing value in only six patients. Complete resection was achieved by lesionectomy or focal corticectomy in nine patients. Histopathologically, six patients had FCD type IIb and three had FCD type IIa. Next‐generation sequencing analysis of DNA extracted from lesion‐enriched (micro‐dissected) tissue from five patients with FCD type II led to the identification of a germline frameshift insertion in DEPDC5, introducing a premature stop in one patient. Eight out of nine patients with available follow‐up were completely seizure‐free (Engel Class IA) after a mean follow‐up period of six years. Conclusion. Our results confirm previous studies classifying difficult‐to‐localize BOS‐FCD into the emerging spectrum of FCD ILAE type II mTORopathies. Further studies with large patient numbers and ultra‐deep genetic testing may help to bridge the current knowledge gap in genetic aetiologies of FCD.     

Pregabalin in partial seizures: a pragmatic 21‐week,open‐label study (PREPS)

Background and purpose: Pregabalin has demonstrated efficacy in controlled trials as adjunctive treatment in patients with refractory seizures. Methods: This open‐label, 21‐week study in adults with at least two partial seizures in the last 2 months, who were inadequately controlled with one to three antiepileptic drugs, evaluated pregabalin 150–600 mg/day (dosed twice daily). The study comprised a prospective or retrospective 8‐week baseline phase, and 9‐week dose optimization and 12‐week maintenance periods. The primary assessment was the mean percentage change in 28‐day seizure frequency between baseline and end‐point (last 12 weeks of treatment, last observation carried forward, modified intention‐to‐treat population). Results: Four hundred and seventy‐six patients from Europe were included in this study (51% men; mean age/epilepsy duration 40.1/24.1 years). The median baseline seizure frequency was 5.5/28 days. Amongst the patient population, 78% completed the 21‐week treatment period; 7% discontinued for lack of efficacy and 12% because of adverse events (AEs). The mean last pregabalin dose was 359 mg/day. The mean (95% CI) reduction in seizure frequency was 36% (31%; 41%). The median reduction was 33%, and 39% of patients had a ≥50% reduction in seizure frequency. There were 19% and 8% of patients free of seizures during their last 4 and 12 weeks of treatment, respectively. The three most common AEs were dizziness (17%), somnolence (13%) and weight increase (13%). Conclusions: This open‐label study of pregabalin demonstrated efficacy that was consistent with that observed in previous controlled epilepsy trials. Pregabalin was well tolerated. The AE profile was also consistent with that reported in previous trials.     

One‐year clinical experience of perampanel in Spain: a multicentre study of efficacy and tolerability

Perampanel, a non‐competitive antagonist of the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole‐propionic acid receptors, is the most recent antiepileptic drug available in Spain, marketed in January 2014. It was initially approved by the European Medicines Agency as adjunctive treatment for partial‐onset seizures in patients 12 years and older, but recently also for primary generalized tonic‐clonic seizures. Although clinical trials provide essential information about the drug, they do not reflect daily clinical practice. This retrospective study shows the initial experience with perampanel in 11 Spanish hospitals during its first year post‐commercialisation. All patients who started perampanel treatment were included, but efficacy and tolerability were only assessed in those patients with a minimum follow‐up period of six months. In total, 256 patients were treated with perampanel before September 2014, and 253 had an observational period of one year. After six months, 216/256 patients (84%) continued on perampanel and 180/253 (71.1%) completed one year of treatment. The mean number of previous antiepileptic drugs used was 6.83 and the median number of concomitant antiepileptic drugs was 2. The mean perampanel dose was 7.06 mg and 8.26 mg at six and 12 months, respectively. The responder rate was 39.5% and 35.9% at both follow‐up points, respectively. Adverse events were experienced by 91/253 (35.5%) and resulted in withdrawal in 37 (14.6%). The most common adverse events were somnolence, dizziness, and irritability. We found no significant differences between concomitant use of enzyme‐inducing and non‐inducing antiepileptic drugs, regarding efficacy, adverse effects, or withdrawals. Irritability was not influenced by concomitant use of levetiracetam, relative to other drugs, but was more frequently observed in patients with a history of psychiatric problems or learning disabilities.     

Efficacy and safety of lacosamide as an adjunctive therapy for refractory focal epilepsy in paediatric patients: a retrospective single‐centre study

Aim. Lacosamide is an antiepileptic drug approved for the treatment of focal epilepsy in adult patients. The aim of this observational study was to review our centre's experience with lacosamide and to characterize its effectiveness and tolerability as an adjunctive antiepileptic drug in a retrospective cohort of children with refractory focal epilepsy. Methods. We retrospectively reviewed the medical records of 22 patients who received lacosamide from November 2009 to April 2014 at the CHU Ste‐Justine, University of Montreal. Treatment responders were defined as children with a ≥50% reduction in seizure frequency compared to baseline, and this was determined three months after the initiation of treatment and at the last follow‐up visit. Results. We included 14 boys and eight girls with a mean age of 12.9 years (SD: 5.2; range: 5.2–20.7 years) at the initiation of treatment. The average length of follow‐up was 11.9 months. Patients had previously received an average of 7.5 antiepileptic drugs. The mean number of concomitant antiepileptic drugs was 2.3. The mean initial and maintenance doses were 2.9 and 8.4 mg/kg/d, respectively. Thirteen (59%) and ten (45%) patients were responders after three months of treatment and at the last follow‐up visit, respectively. One became seizure‐free. Adverse effects were reported in 11 patients and none were severe. Responders and non‐responders were identical with respect to all studied parameters except gender, with the proportion of responders being greater in girls than in boys (75% vs 29%; p=0.035). Conclusion. Our study adds evidence that lacosamide appears to be a safe and effective adjunctive therapy for children with refractory focal epilepsy.