Percentage Of Seizure-free Patients Research Articles

BRIVA-ONE study: 12-month outcomes of brivaracetam monotherapy in clinical practice.

This study investigated the effectiveness and tolerability of brivaracetam (BRV) monotherapy in a large series of patients with epilepsy. This was a multicenter, retrospective, observational, non-interventional study in 24 hospitals across Spain. Patients aged ≥18 years who started on BRV monotherapy, either as first-line or following conversion, at least 1 year before database closure were included. Patients were evaluated at baseline and at 3, 6 and 12 months after initiation of BRV monotherapy, in accordance with usual clinical practice at these centers. Data were collected retrospectively from patients' individual charts by participating physicians. The primary effectiveness and safety endpoints were the percentage of seizure-free patients 1 year after initiation of BRV monotherapy and the proportion of patients reporting adverse events (AEs) over the complete follow-up period. Retention rates and subpopulation analysis (levetiracetam switchers, elderly and different etiologies) were also investigated. A total of 276 patients were included (48 with BRV as first-line monotherapy and 228 who converted to BRV monotherapy). The overall retention rate in monotherapy at 12 months was 89.9% (87.5% for first-line monotherapy group; 90.4% for conversion-to-monotherapy group). Seizure-freedom rates at 12 months were 77.8% (75% for first-line monotherapy group; 78.4% for conversion-to-monotherapy group). AEs occurred in 39.5% of patients at 12 months (35.4% for first-line monotherapy group; 40.4% for conversion-to-monotherapy group). Most AEs were mild-to-moderate. The most frequent AEs were irritability (12.3%) and dizziness (10.1%). The most frequent AEs leading to BRV withdrawal were dizziness (1.8%) and memory problems (1.4%). Similar outcomes in terms of effectiveness and tolerability of BRV monotherapy were observed in patients switching from levetiracetam, those with different epilepsy etiologies, and elderly patients. BRV was effective and well tolerated both as first-line monotherapy and following conversion to monotherapy in a real-world setting of patients with epilepsy. The goal of the medical treatment of epilepsy is to ensure best possible patient quality of life, by maximizing seizure control and minimizing medication toxicity. Brivaracetam (BRV) is a new-generation epilepsy treatment that is well tolerated by patients. In our study, monotherapy with BRV reduced seizures in patients who had not received other treatments and in patients who switched from a previous treatment to BRV monotherapy. BRV was well tolerated and also effective in sensitive patients (i.e., the elderly and those who had epilepsy caused by a brain tumor or a brain injury).

Alzemon: a prospective follow-up study of eslicarbazepine acetate monotherapy in patients with newly diagnosed epilepsy

Eslicarbazepine acetate is a novel sodium channel blocker for use in the treatment of focal onset seizures. Prospective studies on its effectiveness in monotherapy in patients with newly diagnosed partial epilepsy in routine clinical practice are scarce. To evaluate the effectiveness of eslicarbazepine as initial monotherapy in patients with newly diagnosed partial epilepsy in routine clinical practice. A prospective, multicentre, post-authorisation study. Patients with newly diagnosed partial epilepsy aged 18 years or older without previous treatment were included. The efficacy variables were: percentage of seizure-free patients, responders and reduction in monthly frequency of seizures. The safety variables analyse the 12-month retention rate and the occurrence of adverse effects. Fifty-three patients were included. The retention rate was 77.4%. At the end of the observation period, 83% of patients were seizure-free and 92.5% had reduced their baseline frequency by 50% or more. In addition, 68% of the patients reported some adverse effect and 7.5% of them dropped out of the study for this reason. The effectiveness analysis of the subgroup of patients aged 65 years or more showed no differences with respect to the overall population. Eslicarbazepine monotherapy in patients with newly diagnosed partial epilepsy, both in the general population and in the population over 65 years old, is effective and safe in routine clinical practice.

Effectiveness and safety of perampanel as early add-on treatment in patients with epilepsy and focal seizures in the routine clinical practice: Spain prospective study (PERADON)

ObjectivePerampanel (PER) has been shown to be effective as an adjunctive therapy for controlling refractory focal-onset seizures (FOS). However, the information as early add-on for the treatment of FOS in the clinical practice is still scarce and must be further assessed. MethodsAn observational prospective study was conducted to evaluate the effectiveness of early add-on PER, assessed as 50% responders (seizure frequency reduced by at least 50% during the last 3 months as compared with baseline) rate at 6 and 12 months, in patients with FOS in the routine clinical practice of Spain. ResultsOne hundred and thirteen patients (mean age: 40.3 years, 51.3% male) with FOS received PER as early add-on (1st add-on: 37.2% and 2nd: 62.8%) for a mean exposure of 11 months (mean PER dose: 6.3 mg/day at month 12). At 6 months, 50.4% and 20.4% of the patients were responders and seizure-free (respectively) relative to baseline (3 months prior to PER initiation), and at 12 months, 68.1% and 26.5% of the patients were responders and seizure-free (respectively), relative to baseline (3 months prior to PER initiation). The retention rate at 6 and 12 months was 83.2% and 80.5%, respectively. The percentage of seizure-free patients at 12 months was significantly (p = 0.033) higher when PER was added as first vs. second add-on. The number of concomitant antiepileptic drugs (AEDs) was significantly reduced from baseline to 6 and 12 months (p = 0.001). Treatment was simplified in 23.9% of patients at the end of the observation period. Drug-related adverse events (AEs), most mild or moderate, were reported in 30.1% of patients, with irritability (8%) and dizziness (7.1%) as the most frequent ones. ConclusionsThis is the first observational, prospective study to evaluate efficacy and safety of early adjunctive treatment with PER in patients with focal epilepsy at 12 months. Perampanel demonstrated a good efficacy and safety profile when used at a median dose of 6 mg/day, regardless of the combination with other AEDs. Adverse events were mild or moderate, with dizziness being the most frequent one.

Adjunctive perampanel in refractory epilepsy: Experience at tertiary epilepsy care center in Tours.

The purpose of this study was to evaluate the effectiveness and safety of PER as add-on treatment in patients with severe refractory epilepsy with a particular focus on patients with learning disability and/or psychiatric comorbidity. We pooled retrospective data from adult patients with refractory epilepsy prescribed perampanel from a tertiary center in France between 1st May 2014 and 3rd June 2015. Data collection was done on February 2016. One hundred and one patients were included (mean age: 41.2years, 37.6% with learning disability and 49.5% with psychiatric comorbidity). Mean retention was 8.1months (range: 14days to 17months). On final evaluation, a >50% reduction in seizure frequency was reached in 41.6% of patients, and 7 patients (6.9%) became seizure-free. Sixty-three patients (62.4%) experienced adverse effects. The most common adverse effects were irritability, asthenia, aggression, and sedation. Efficacy, retention of treatment, and safety were equally similar in patients with learning disability or psychiatric comorbidity as for those without. The only significant difference was in percentage of seizure-free patients: 11.1% in the group without learning disability compared with 0% in the group with (p=0.043). Adjunctive PER can achieve clinically meaningful improvement, or even seizure freedom, in more than one-third of patients suffering from severe refractory epilepsies. It seems similarly safe and effective in the subgroup of these patients with learning disability or with psychiatric comorbidity. However, the rate of psychiatric side effects is high,; of note, we asked both patient and caregivers at each visit especially focusing on psychiatric side effects. Patients, caregivers, and families should be informed of potential psychiatric/behavioral risks associated with taking perampanel especially during the initial titration period.

Clinical dissection of childhood occipital epilepsy of Gastaut and prognostic implication.

Our aim was to describe the clinical and electrical features and the long-term evolution of childhood occipital epilepsy of Gastaut (COE-G) in a cohort of patients and to compare long-term prognosis between patients with and without other epileptic syndromes. This was a retrospective analysis of the long-term outcome of epilepsy in 129 patients with COE-G who were referred to 23 Italian epilepsy centres and one in Austria between 1991 and 2004. Patients were evaluated clinically and with electroencephalograms for 10.1-23.0 years. The following clinical characteristics were evaluated: gender, patient age at seizure onset, history of febrile seizures and migraine, family history of epilepsy, duration and seizure manifestations, circadian distribution and frequency of seizures, history of medications including the number of drugs, therapeutic response and final outcome. Visual hallucinations were the first symptom in 62% and the only manifestation in 38.8% of patients. Patients were subdivided into two groups: group A with isolated COE-G; group B with other epileptic syndromes associated with COE-G. The most significant (P < 0.05) difference concerned antiepileptic therapy: in group A, 45 children responded to monotherapy; in group B only 15 children responded to monotherapy. At the end of follow-up, the percentage of seizure-free patients was significantly higher in group A than in group B. Childhood occipital epilepsy of Gastaut has an overall favourable prognosis and a good response to antiepileptic therapy with resolution of seizures and of electroencephalogram abnormalities. The association of typical COE-G symptoms with other types of seizure could be related to a poor epilepsy outcome.

Early add-on treatment vs alternative monotherapy in patients with partial epilepsy.

The aim of this study was to evaluate the impact of two different therapeutic strategies in patients with partial seizures who were intractable to the first prescribed antiepileptic drug (AED); alternative monotherapy vs early add-on treatment. We conducted an open, cluster-randomised, prospective, controlled trial in patients with persistent partial seizures, despite treatment with one AED, who were never administered any other AEDs. Neurologists were randomised to two strategies: in group A, an alternative monotherapy with a second AED was employed; in group B, add-on treatment with a second AED was employed. The primary outcome was the percentage of seizure-free patients during a two-month period after six months of treatment. The secondary outcomes were: (i) the percentage of patients achieving a 50% reduction in the number of seizures at six months; (ii) the quality of life based on the Quality Of Life In Epilepsy scale; and (iii) tolerability. A total of 143 neurologists were included and randomised, and 264 patients were evaluated. At six months, the primary outcome was 51% in group A and 45% in group B (p=0.34). The percentage of patients achieving a 50% reduction in the number of seizures at six months was 76% in group A and 84% in group B (p=0.53). The quality of life and the tolerability did not significantly differ between the two groups. Alternative monotherapy or early treatment initiation with another AED drug resulted in similar efficacy, and the side effects associated with monotherapy and combined therapies were similar, which suggests that individual susceptibility is more important than the number and burden of AEDs used.

Long-term surgical outcomes in patients with drug-resistant temporal lobe epilepsy and no histological abnormalities

IntroductionReports on surgical outcomes in patients with drug-resistant temporal lobe epilepsy without histological abnormalities are scarce. MethodsRetrospective review of data from patients with drug-resistant temporal lobe epilepsy and no histopathological alterations who underwent anterior mesial temporal lobectomy. We analysed the following variables: age, sex, age at seizure onset, age at surgery, time elapsed between diagnosis and the date of the surgery, follow-up time, and classification according to the Engel rating scale. ResultsFrom a database of 256 temporal lobectomies, 21 were identified as meeting the inclusion criteria. The average age upon diagnosis of epilepsy was 8.3 years and average age at time of surgery was 28.6 years. The mean time elapsed between diagnosis and surgery was 20.2 years. After a mean follow-up of 6.5 years, 90.5% of the patients showed favourable outcomes (classes i and ii) and 42.9% were seizure-free (class IA). Comparative analysis of the variables revealed that average age at seizure onset was the only statistically significant difference between groups, with age at onset being lower in patients with favourable outcomes. ConclusionAlthough long-term surgical outcomes were favourable for a large majority of patients, the percentage of seizure-free patients is lower than in patients with lesional epilepsy and comparable to that previously reported in the literature.

Resultados quirúrgicos a largo plazo en pacientes con epilepsia fármaco-resistente del lóbulo temporal sin anormalidades histológicas

IntroductionReports on surgical outcomes in patients with drug-resistant temporal lobe epilepsy without histological abnormalities are scarce. MethodsRetrospective review of data from patients with drug-resistant temporal lobe epilepsy and no histopathological alterations who underwent anterior mesial temporal lobectomy. We analysed the following variables: age, sex, age at seizure onset, age at surgery, time elapsed between diagnosis and the date of the surgery, follow-up time, and classification according to the Engel rating scale. ResultsFrom a database of 256 temporal lobectomies, 21 were identified as meeting the inclusion criteria. The average age upon diagnosis of epilepsy was 8.3 years and average age at time of surgery was 28.6 years. The mean time elapsed between diagnosis and surgery was 20.2 years. After a mean follow-up of 6.5 years, 90.5% of the patients showed favourable outcomes (classes i and ii) and 42.9% were seizure-free (class IA). Comparative analysis of the variables revealed that average age at seizure onset was the only statistically significant difference between groups, with age at onset being lower in patients with favourable outcomes. ConclusionAlthough long-term surgical outcomes were favourable for a large majority of patients, the percentage of seizure-free patients is lower than in patients with lesional epilepsy and comparable to that previously reported in the literature.

Efficacy of Topiramate in Adult Patients with Symptomatic Epilepsy

Topiramate is a newer generation antiepileptic drug with a wide range of antiepileptic efficacy as monotherapy or as adjunctive therapy, and which has shown positive activity in intractable epilepsy and newly diagnosed epilepsy. Topiramate has also been shown to exert good seizure control with a low incidence of adverse effects in brain tumour-associated epilepsy. However, there have been few reports on the efficacy of topiramate in the treatment of symptomatic epilepsy of varying aetiologies. The aim of the present study was to evaluate the efficacy of topiramate in the treatment of adult patients with symptomatic epilepsy of various aetiologies. This was an open-label, long-term, retrospective observation. 227 patients with symptomatic epilepsy (110 male, 117 female) were enrolled into this study. The underlying aetiologies included low-grade brain tumour, head trauma, cerebrovascular diseases, infection, diabetes mellitus, hydrocephalus and parasitosis. Topiramate was titrated up to a target dosage of 200 mg/day and maintained for at least 1 year. Response to topiramate was defined as > or = 50% reduction in seizure frequency compared with baseline. Seizure free was defined as no seizure occurring during 1 year of topiramate therapy. 157 (69.2%) patients were responders and 124 (54.6%) patients were seizure free with topiramate administration. Responders by subgroup included 40 patients (74.0%) with low-grade brain tumour, 32 (55.2%) with trauma, 30 (90.9%) with cerebrovascular disease, 21 (55.3%) with infection, 18 (81.8%) with diabetes, 12 (85.7%) with parasitosis and 4 (50.0%) with hydrocephalus. The percentage of seizure-free patients by subgroup was 61.0% with brain tumours, 31.0% with trauma, 78.8% with cerebrovascular disease, 44.7% with infection, 59.0% with diabetes, 85.7% with parasitosis and 50.0% with hydrocephalus. The incidence of adverse effects was 36.1%. The most commonly reported adverse effects were weight loss, memory impairments, paraesthesia, headache and dizziness; most were mild to moderate in severity and transient. Sixty-eight (30.0%) patients withdrew from topiramate treatment in this study: topiramate was discontinued in 56 patients because of lack of efficacy and in 12 patients because of adverse effects. At the end of the study, 109 patients received topiramate monotherapy, including 52 newly diagnosed patients and 57 subjects who transferred to topiramate monotherapy successfully; another 118 patients received add-on topiramate therapy. The percentage of patients responding to topiramate was 85.3% in the monotherapy group and 54.2% in the topiramate add-on therapy group; the percentage of seizure-free patients was 68.8% in the topiramate monotherapy group and 41.5% in the topiramate add-on therapy group. When administered either as a single drug or as an add-on drug, topiramate is effective and well tolerated in adult patients with symptomatic epilepsy of various aetiologies.

Évaluation à long terme des déconnexions hémisphériques

Hemispheric disconnection has been largely proposed for patients with severe epilepsy associated with a congenital or acquired hemispheric cerebral pathology. The classical procedure of anatomical hemispherectomy was progressively abandoned by neurosurgeons in order to avoid postoperative complications since then hemispherotomy techniques have been developed. Globally, with hemispheric disconnection, the rate of patients becoming seizure-free has been between 50 and 80%. The factors affecting seizure control have not been completely elucidated, but several authors suggested that differences in etiology as well as the hemispheric disconnection technique used may partially explain this variability. The percentage of seizure-free patients is higher with hemispherotomy techniques and in the group of patients with Rasmussen encephalitis, Sturge-Weber syndrome, and vascular insults. Depending on overall long-term progression, there is an improvement compared to preoperative status even if children exhibit heterogenous abilities. The lowest scores are observed for motor skills but communication and socialization are relatively well-preserved and strongly related to the duration of epilepsy: the longer the duration, the lower the scores were. Neuropsychological outcome following hemispheric disconnection makes it possible to study the development of hemispheric specialization during infancy and to provide information on cognitive recovery. Cerebral reorganization has been proved to exist in motor and language recovery. Ipsilateral corticospinal pathways seem to be involved in the movement of hemiplegic limbs. Everyday language can be supported by both hemispheres, but there is an early hemispheric specialization of the left hemisphere according to metaphonologic abilities.

Topiramat - Initiale Monotherapie bei älteren Patienten mit Epilepsie

In this open-label, observational study, the safety and tolerability of topiramate monotherapy as well as changes in seizure frequency in elderly individuals (age ≥ 65 years) with newly or recently diagnosed epilepsy were documented. The study was conducted in 55 German neurological private practices and outpatient clinics between October 2003 and March 2005. A total of 145 patients were involved. A standardised case report form was used to document demographic data, history, epileptic syndrome, aetiology, number of concomitant medications, dose of topiramate, additional anticonvulsants, seizure frequency and adverse events at baseline, and at follow-up visits after 3 and 6 months, respectively. Duration since epilepsy diagnosis was approximately one year. Mean age was 73 years and 71 patients were women. 79 patients had symptomatic or cryptogenic focal epilepsy, 10 patients had cryptogenic or symptomatic generalized epilepsy, 56 patients were not classified. 93 % patients had a least one concomitant disease and about 90 % had at least one other medication. Topiramate doses ranged between 50 and 100 mg per day in most patients. At the end of the study, 40.7 % patients were seizure-free. In the per protocol group, the percentage of seizure free patients was slightly higher (42.7 %); the median duration of seizure freedom in this group was 185 days (range: 168 - 263). 5.5 % of patients had at least one adverse event (AE), and two patients discontinued treatment due to an AE. Our observational study is consistent with the results from recent clinical trials that topiramate in a naturalistic setting is well tolerated in elderly patients and renders a high proportion of patients seizure free.

Antiepileptic Drugs: Adult

Abstract 1 Alaa M. Ahmad, 1 Frank D. Boudinot, 2 William H. Barr, 3 Ronald C. Reed, and 2 William R. Garnett ( 1 Pharmaceutics, Virginia Commonwealth University, Richmond, VA ; 2 Pharmacy, Virginia Commonwealth University, Richmond, VA ; and 3 Neuroscience, Abbott Laboratories Inc., Abbott Park, IL ) Rationale: Clinicians rely primarily on total valproic acid (VPA) concentrations for therapeutic monitoring. However, due to nonlinear plasma protein binding of VPA, dose titration is complicated by disproportionality between the total drug concentration and dose. The purpose of this report was to develop a nomogram for VPA based on total drug concentrations. Methods: Nine healthy volunteers were administered 500, 750 and 1000 mg VPA in a dose escalation study. Plasma protein binding of VPA was characterized for each volunteer in vitro. Results: A one-site saturable binding model provided an adequate description of the binding of VPA to albumin and yielded (mean,% standard error) 2.3 (4.5%) binding sites (N) and an equilibrium association constant (KA) of 6.7 (17.9%) (L/mM). Predictions for the increase in total concentration observed with dose escalation were based on individual and population pharmacokinetic parameters. There weren't significant statistical differences between the predictions based on individual and population estimates (based on root mean square error and mean absolute error). Conclusions: Using population estimates, a dosing nomogram for VPA was constructed. To minimize the risk of achieving toxic drug concentrations, the dose should not be increased more than 2 fold at a time. The nomogram should be used in conjunction with patient history and clinical response to aid clinicians in making informed decisions about dose-adjustments. The nomogram can be used for all VPA preparations and regardless of enzyme inducing or inhibiting co-medications. (Supported by Virginia Commonwealth University.) (1) [(A) Percent reduction of the number of seizures; (B) Percentage of seizure-free patients (ITT)]

Long-term follow-up of seizures associated with cerebral arteriovenous malformations. Results of therapy.

Of 115 patients with angiographically demonstrated cerebral arteriovenous malformations (AVMs), seizures occurred in 66 (57%), all of whom had supratentorial AVMs. Seizures were the initial manifestations in 36 patients. In 14 patients seizures developed within 30 days of hemorrhage or surgical resection; in 16 others seizures started within 0.5 to 16 years after hemorrhage or resection. Seizures were infrequent in the majority of patients; in only nine (16%) were they incapacitating. Among 46 patients observed from two to 36 years, 23 (50%) were seizure free for a minimum of two years at follow-up. Neurological deficits on examination and previous occurrence of hemorrhage did not adversely affect seizure control. No significant difference was found between the percentage of seizure-free patients in the medical and surgical groups at follow-up. Irrespective of treatment method, seizures starting within 30 days of hemorrhage or resection had the best prognosis.