Efficacy and tolerability of zonisamide as add‐on in brain tumor‐related epilepsy: preliminary report

Background –  Zonisamide (ZNS) is an antiepileptic drug (AED) with broad spectrum action that demonstrated a good efficacy in controlling seizures as add‐on in adult and pediatric epilepsy. To date there have been no studies on ZNS in patients with brain tumor‐related epilepsy (BTRE). Aim of the study –  To evaluate efficacy and tolerability of ZNS as add‐on in BTRE. Methods– We followed six patients suffering from BTRE who had already been treated with other AEDs and who had had not experienced adequate seizure control. Three patients underwent chemotherapy while being treated with ZNS. Mean duration of follow‐up was 8 months. Results –  Mean seizure number in the last month prior to the introduction of ZNS had been 27.7/month. ZNS mean dosage was of 283.3 mg/day. At last follow‐up, the mean seizure number was reduced to 8.8/month. Responder rate was 83.3%.Two patients discontinued the drug because of side effects. There were no other reported side effects. Conclusions –  Preliminary data on the use of ZNS in add‐on in patients with BTRE indicate that this drug may represent a valid alternative as add‐on in this particular patient population. However, larger samples are necessary to draw definitive conclusions.     

Quality of life,mood and seizure control in patients with brain tumor related epilepsy treated with lacosamide as add-on therapy: A prospective explorative study with a historical control group

ObjectiveBrain tumor-related epilepsy (BTRE) is often drug resistant and patients can be forced to take polytherapy that can adversely affect their quality of life (QoL). Lacosamide (LCM) is a new antiepileptic drug (AED) used as adjunctive therapy in patients with partial seizures with or without secondary generalization, with a favorable pharmacokinetic profile that seems to be effective and well tolerated.Therefore it represents a possible therapeutic choice for patients with BTRE. We propose a prospective study with a historical control group to evaluate the effect of LCM as add-on therapy on seizure control and quality of life in patients with BTRE. This study has been designed to test the superiority of Lacosamide over Levetiracetam as an add-on. We compared a prospective cohort of 25 patients treated with Lacosamide with a historical control group (n = 19) treated with Levetiracetam as an add-on.MethodsWe recruited 25 adult patients (M 18, F 7; mean age 41.9) affected by BTRE with uncontrolled partial-onset seizures treated with AED polytherapy. We added LCM as an add-on. Patients were evaluated at baseline, after 3 months and at 6 months.This population has been compared with a historical control group of 19 BTRE adult patients (M 13, F 6; median age 48.0, range: 28–70) with uncontrolled partial-onset seizures treated with LEV as add-on.The patients underwent QoL, mood and adverse events tests (Adverse Event Profile-AEP) and evaluation of seizure frequency.ResultsTwelve patients had high grade gliomas, and thirteen had low grade gliomas. During follow-up, thirteen patients underwent chemotherapy, three radiotherapy and five patients had disease progression. Nine patients had simple partial seizures, eight had complex partial seizures, and eight had secondary generalized seizures. Fifteen patients were in monotherapy and ten in polytherapy with AEDs. LCM was added up to reach the maximum dosage of 400 mg/die (mean final dose 300 mg/die). Four patients dropped out due to poor compliance and 1 for inefficacy.In the historical control group treated with LEV (mean final dose 2000 mg/die) 12 patients had high-grade gliomas, and 7 had low grade gliomas. Thirteen patients were in monotherapy and 6 in polytherapy with AEDs.In the 22 patients evaluable of 25 patients treated with LCM, we observed at final follow-up 7 patients seizure free, 12 with a significant reduction of seizures ≥ 50%, 2 stable and 1 patient with number of seizures increased.Mean seizure frequency at baseline compared with baseline period: the mean number of seizures significantly decreased from baseline (9.4) to final follow-up (1.2) (P = 0.005). The Responder Rate was 86.4%.Comparing responder rate of 22 evaluable patients with LCM with responder rate of 19 patients with LEV we didn't observe significant differences (p = 0.31).In our patients treated with LCM we didn't observe significant difference at 3 and 6 months in QoL tests results; we observe a significant reduction in the mean score of Karnofsky Performance Status (KPS) and Barthel Index (BI) between baseline and 6 months of follow-up (KPS p = 0.003; BI p = 0.007).No clinical side effects were observed.ConclusionComparing the LCM with the historical group treated with LEV in add-on, we observed that LCM seems to have a higher clinical efficacy than LEV.In our patients, we did not observe any significant changes in QoL tests, indicating stability in all quality of life domains explored, despite the objective worsening in their functional status. Although this is a small series with a relatively short follow-up, our data indicates that LCM in add-on in patients with BTRE appears to be as effective as LEV in add-on, without impact on mood and quality of life.     

Lacosamide in patients with temporal lobe epilepsy: An observational multicentric open-label study

PurposeThe aim of this study was to evaluate the efficacy and tolerability of lacosamide (LCM) both as add-on therapy and monotherapy in patients with temporal lobe epilepsy (TLE) based on an observational, prospective, multicenter study.MethodsWe enrolled 100 patients (mean age: 43.4 ± 12.53 years, 57 females) with nonlesional TLE and TLE with hippocampal sclerosis (HS) that did not respond to the first drug and who were referred to epilepsy centers of the University of Catanzaro, University of Palermo, IRCSS Neuromed of Pozzilli, and Otto-von-Guericke University of Magdeburg. In this open-label, multicenter trial, patients were initiated on oral LCM as add-on therapy to first AED monotherapy or as a later add-on to two concomitant AEDs. Seizure frequency changes and adverse events were recorded for at least six months after LCM was added.ResultsFourteen patients dropped out because of positive MRI findings other than HS. Patients received LCM at 200–400 mg/day. Fifty-eight out of these 86 patients with seizures that were previously drug-resistant had reduced seizure frequency after introduction of LCM. Forty-five out of 86 patients were classified as responders (12 were seizure-free, 33 achieved a reduction > 50%). Interestingly, five patients out of 86 achieved seizure freedom for at least one year and progressively switched to monotherapy with LCM, and all five remained seizure-free at follow-up (6–48 months).ConclusionsOur results may suggest that LCM at doses of 200 to 400 mg/day reduces seizure frequency in adults with TLE regardless of the presence of HS, and that it may be considered as a first add-on treatment for patients with pharmacoresistant TLE.     

Clinical management of elderly patients with epilepsy; the use of lacosamide in a single center setting

IntroductionLacosamide (LCM) is a third-generation antiepileptic drug (AED) for which there is limited experience in the treatment of elderly patients with epilepsy. This study was performed to evaluate the use of LCM in this particular patient group, focusing on its tolerability and effectiveness. This is a retrospective, single-center study, in patients over 60 years old treated with LCM between 1/2010 and 5/2015. Altogether, 233 elderly patients receiving LCM were identified; of these, 67 fulfilled the inclusion criteria, i.e., LCM administered for at least 2 weeks.ResultsLacosamide was initiated for acute seizure disorders (prolonged complex partial seizures, recurrent seizures, or status epilepticus) in 54 patients (81%) and for chronic epilepsy in 13 patients in an outpatient setting. The mean follow-up period for LCM treatment was 14 months. The mean daily dose of LCM at the end of follow-up was 368 mg (range: 100–600) for those 57 patients that continued treatment. Ten patients (15%) stopped LCM treatment but none because of lack of efficacy and only three patients (4%) because of side effects. The most frequent side effects were dizziness, fatigue, and tremor.ConclusionsLacosamide was well tolerated even at relatively high doses and in combination therapy.     

NEOPLASM study: Real-life use of lacosamide in patients with brain tumor-related epilepsy

BackgroundThe choice of antiepileptic drug (AED) therapy in patients with brain tumor-related epilepsy (BTRE) is complicated, and there are a lack of robust clinical trial data to date.MethodsThe NEOPLASM (Neuroncologic Patients treated with LAcoSaMide) study was a 6-month, multicenter, retrospective, observational study in patients with BTRE treated with lacosamide. Patients were started on lacosamide because of a lack of efficacy or adverse events (AEs) with prior AEDs or suitability versus other AEDs, according to clinical practice. The primary efficacy variable was the seizure-free rate at 6 months. Safety variables included the proportion of patients with an AE and the proportion with an AE that led to discontinuation.ResultsOverall, 105 patients from 14 hospital centers were included in the analysis. Treatment with lacosamide for 6 months resulted in a 30.8% seizure-free rate, and 66.3% of patients had a ≥ 50% seizure reduction (responders). In the subset of patients included because of a lack of efficacy with prior AEDs, seizure-free rates were 28.0%, and 66.7% of patients were responders. No statistically significant differences in efficacy were observed according to the mechanism of action or enzyme-inducing properties of concomitant AEDs. Adverse events were reported by 41.9% of patients at 6 months, and 4.7% of them led to discontinuation. The most common AEs were somnolence/fatigue and dizziness. Notably, 57.1% of the patients who were switched to lacosamide because of AEs with their previous therapy did not report any AE at 6-month follow-up.ConclusionsIn this open-label, observational study, lacosamide appeared to be effective and well tolerated in a large population of patients with BTRE. Lacosamide may therefore be a promising option for the treatment of patients with BTRE.     

Clinical experience with oral lacosamide as adjunctive therapy in adult patients with uncontrolled epilepsy: a multicentre study in epilepsy clinics in the United Kingdom (UK)

IntroductionLacosamide (LCS) is a new antiepileptic drug (AED) licensed in the European Union (EU) and United States (US) in 2008.AimsTo evaluate the efficacy and tolerability of add-on LCS in an out-patient epilepsy clinic setting to obtain useful information for everyday practice.MethodsWe pooled data retrospectively from the case note of patients with refractory epilepsy in whom LCS had been prescribed in 19 hospitals across the United Kingdom.ResultsFour hundred and three patients were included (mean age 41.9 years, 50.6% women, 18.1% with learning disabilities (LD)). Mean follow-up (FU) was 11.6 months (range one day to 42 months). Most patients (86.9%) presented with symptomatic partial epilepsy (SPE) and 80% were taking two or more antiepileptic drugs (AEDs) when LCS was added (mean 2, range 0–4). Retention rates were 80% at six months, 68% at one year and 45% at two years. The efficacy of LCS was evaluated at three months and at the final FU. At three months one hundred and eight patients (31.1%) reported ≥50% seizure reduction and 32 (9.2%) were seizure free. At the final FU 102 (37.5%) reported ≥50% seizures reduction and 28 (9.8%) were seizure free.One hundred and ninety three patients (48.7%) reported adverse effects (AEs). The most frequent were sedation and dizziness, followed by nausea. Lacosamide was discontinued in 150 patients (38%), 60 due to AEs alone.ConclusionLCS appears to be an effective and safe AED when used as adjunctive therapy in patients with refractory partial epilepsy.     

Prospective audits with newer antiepileptic drugs in focal epilepsy: Insights into population responses?

Despite the availability of a wide range of new antiepileptic drugs (AEDs), there is little evidence that their introduction has substantially altered outcomes. This paper reviews data from 5 consecutive prospective audits with new AEDs using similar methodology. Prospective audits with topiramate (TPM; n = 135), levetiracetam (LEV; n = 136), zonisamide (ZNS; n = 141), pregabalin (PGB; n = 135), and lacosamide (LCM; n = 160) were undertaken in treated patients with uncontrolled partial-onset seizures. Follow-up continued until one of four endpoints was reached: seizure freedom for ≥ 6 months on unchanged dosing; ≥ 50% reduction (responder) in seizure frequency on the highest tolerated dose compared with baseline; < 50% seizure frequency reduction (marginal response) compared with baseline in patients wishing to continue treatment with the new AED; or withdrawal due to lack of efficacy, side effects, or both. A greater proportion of seizure-free patients occurred with LEV (23.5%), LCM (21.9%), and TPM (20.7%) than with ZNS (12.8%) and PGB (10.4%). A higher percentage discontinued treatment with ZNS (41.8%) and PGB (50.4%) than with LEV (32.4%), TPM (31.1%), and LCM (22.5%). Most seizure-free patients responded to the new agent as first or second add-on (TPM 96%; LEV 97%; ZNS 89%; PGB 86%; LCM 97%) often at modest or moderate dosing (TPM 68%, ≤ 200 mg/day; LEV 63%, ≤ 1000 mg/day; ZNS 61%, ≤ 100 mg/day; PGB 86%, ≤ 300 mg/day; LCM 74%, ≤ 200 mg/day). With < 10% of patients discontinuing all AEDs due to lack of efficacy, tolerability was the major factor influencing the number of patients remaining on treatment. Lacosamide was the best (77% patients continued treatment), while PGB was the worst (50% continued treatment) tolerated AED. Overall, seizure freedom was achieved in < 25% of patients in each audit, mainly as a first or second add-on, with best tolerated AEDs producing a higher number of good outcomes. Seizures in very few patients with drug-resistant epilepsy, as defined by the International League Against Epilepsy task force, responded to any of the 5 newer AEDs. These data support the suggestion that the introduction of modern agents has not importantly impacted the outcomes in refractory epilepsy.     

拉考沙胺在儿童难治性癫痫添加治疗的临床效果观察

目的观察考拉沙胺(Lacosamide,LCM)对儿童难治性癫痫添加治疗中的临床疗效。方法收集2019年3月-2019年7月河南省人民医院儿科收治并使用LCM添加治疗的难治性癫痫患儿41例,男21例,女20例,年龄4.6~15.5岁,平均(7.21±3.06)岁。首发年龄0.1~11.0岁,平均(2.82±2.43)岁;病程在0.6~10.0年,平均(4.49±2.34)年。通过自身空白对照研究,口服LCM 6个月,并进行随访,对比观察使用LCM前后的疗效。结果通过空白自身对照,添加LCM药物后,随访时间3、6个月患儿癫痫发作频率显著减少,差异具有统计学意义(P<0.05),且LCM能有效改善患儿精神状态,但对局灶性难治性癫痫发作与全面性难治性癫痫发作改善作用的差异无统计学意义(P>0.05)。结论LCM作为第三代新型抗癫痫药物,添加治疗儿童难治性癫痫能有效地改善癫痫发作频率,并对改善患儿的精神状态具有一定作用。     

Efficacy of Clobazam as Add-On Therapy in Patients with Refractory Partial Epilepsy

PURPOSE: Clobazam (CLB) has an important antiepileptic effect and is less expensive than the new antiepileptic drugs (AEDs), but still has not been considered as first-line drug in the treatment of epilepsy. We evaluated the efficacy of CLB as add-on therapy in patients with refractory partial epilepsy. METHODS: This was an open, retrospective study, conducted at the epilepsy clinic of our university hospital. All patients had chronic epilepsy and were being evaluated for epilepsy surgery. CLB was introduced as add-on therapy (starting with 10 mg/ day) in patients with previous failure of at least two AEDs. Information was obtained from clinical notes and follow-up visits. RESULTS: We evaluated 97 patients, 37 men and 60 women. Ages ranged from 15 to 70 years (mean, 35.8 years). Etiology of epilepsy was hippocampal atrophy in 67 (69%), cortical dysgenesis in nine (9.3%), and other etiologies in nine (9.3%). In 12 (12.3%) patients, the etiology of epilepsy was not identified despite clinical and neurologic investigation. Patients used CLB for a period ranging from 1 month to 7 years and 9 months (mean, 16.7 months) with doses ranging from 10 to 60 mg/day (mean, 29.7 mg/day). Seven (7.2%) patients were seizure free, 48 (49.4%) had > or =50% of improvement in seizure control, 39 (40.2%) had <50% of improvement in seizure control, and in three (3.1%), no data were available. CONCLUSIONS: We conclude that CLB may have efficacy equivalent to that of the new AEDs when used as add-on therapy in patients with refractory epilepsy. CLB should be considered an economic alternative in the treatment of patients with refractory epilepsy.     

Lacosamide in refractory mixed pediatric epilepsy: a prospective add-on study

Lacosamide is a new antiepileptic drug that is currently approved by the US Food and Drug Administration (FDA) for adults 17 years or older for partial-onset seizures. The authors reviewed 21 pediatric patients (<17 years) with various seizure types who were started on oral lacosamide as part of a prospective add-on study as adjunctive therapy for refractory epilepsy. Five patients were excluded due to less than 3 months of meaningful follow-up. Maintenance dosages used ranged from 2.4 to 19.4 mg/kg/d. Eight of 16 (50%) patients had greater than 50% reduction in seizure frequency with adjunctive lacosamide therapy. Eight (50%) patients had generalized epilepsy including 4 with Lennox-Gastaut syndrome. Lacosamide was effective therapy for most seizure types but was particularly effective for partial-onset seizures. Lacosamide was effective in treating 5 of 8 (62.5%) localization-related epilepsies but only 2 of 8 (25%) generalized epilepsies, both Lennox-Gastaut syndrome patients with greater than 90% seizure reduction. None of these very refractory patients remained seizure free.     

Adjunctive lacosamide in clinical practice: sodium blockade with a difference?

Lacosamide (LCM) was licensed in the United Kingdom in 2008 for the adjunctive treatment of partial-onset seizures. It exerts its effect by enhancing sodium channel slow inactivation. This article reports preliminary outcomes with adjunctive LCM in the everyday clinical setting. To date, 113 patients (57 males, 56 females; aged range = 18–74 years, median = 39 years) with uncontrolled partial-onset seizures (monthly frequency range = 1–300, median = 4) have been included in the audit. Patients were taking 1–4 (median = 1) antiepileptic drugs (AEDs), having previously tried 1–12 (median 3) drug schedules. After 12 weeks on stable AED dosing, LCM was added, aiming at an initial target range of 200–400 mg/day. Review took place every 6–8 weeks until one of four endpoints was reached: seizure freedom for ≥ 6 months on a given LCM dose; ≥ 50% (responder) or < 50% (marginal benefit) seizure reduction over 6 months compared with baseline on the highest tolerated LCM dose; withdrawal of LCM because of lack of efficacy, side effects, or both. An endpoint has been reached by 65 (57.5%) patients so far. Seventeen (26.2%) have remained seizure free on a median daily LCM dose of 100 mg (range = 50–300 mg). Patients were more likely to become seizure free when LCM was used as a first add-on (15/36, 41.7%), compared with a later treatment schedule (1/27, 3.7%, P = 0.001). With appropriate dose manipulation, patients taking traditional sodium blockers (5/26, 19.2%) were as likely to become seizure free as those taking AEDs with other mechanisms of action only (11/37, 29.7%). Fifty percent or greater seizure reduction was achieved in an additional 16 (24.6%) patients (1 monotherapy); 18 (27.7%) reported marginal benefit. Two patients were established on LCM monotherapy (one seizure free, one responder). Patients remaining on LCM were as likely to also be taking sodium blockers only (23/27, 85.1%) as AEDs with other mechanisms (26/36, 72.2%). LCM was withdrawn in 14 patients (12.3% of ongoing patients, 21.5% of those at an endpoint; 10 for side effects, 4 for lack of efficacy). The most common side effects leading to withdrawal were sedation, ataxia, and dizziness. Of the 10 with side effects, only 2 patients took concomitant sodium blockers. Patients on sodium valproate were more likely to discontinue LCM (8/21, P = 0.018) than those also taking other AEDs; 5 of the 8 did so because of side effects and 3 because of lack of efficacy. In patients with partial-onset seizures, LCM is an effective and well-tolerated adjunctive AED when combined with appropriate doses of traditional sodium blockers, as well as agents with other mechanisms of action. Seizure freedom was more likely when LCM was used as a first add-on compared with a later treatment schedule. Patients also taking sodium valproate were significantly more likely to discontinue LCM compared with those taking other AEDs. These data suggest that the pharmacological effect of LCM differs importantly from that of AEDs that influence fast inactivation of the sodium channel.     

Lacosamide monotherapy for the treatment of childhood epilepsy with centrotemporal spikes

ObjectiveChildhood epilepsy with centrotemporal spikes (CECTS) is known as age-limited focal epilepsy syndrome in childhood. Lacosamide is a third-generation antiepileptic drug. This study aimed to evaluate the efficacy of lacosamide monotherapy for the treatment of CECTS.MethodsWe enrolled 18 patients (6 girls and 12 boys) who met the following criteria: 1) the age of onset of the seizures was between 3 and 13 years of age; 2) showing at least hemifacial and/or oropharyngeal seizures; 3) interictal discharges in central and/or middle temporal electrodes; 4) no intellectual disability; 5) treatment duration of lacosamide monotherapy over 6 months. We retrospectively collected and analyzed clinical data and treatment information. We evaluated the seizure occurrences during 0–3, 4–6, and 7–12 months from the treatment initiation and the last 6 months of the follow-up. We also evaluated the outcomes as seizure-free if the patients developed no seizures both over 6 months and 3 times of pretreatment mean seizure interval at the last follow-up.ResultsOf the patients, 39%, 67% and 72% were seizure-free during 0–3, 4–6, and 7–12 months from treatment initiation, respectively. Finally, 83% of the patients achieved seizure freedom. Seizure freedom was achieved in 72% during the first 4 months of treatment. All patients continued lacosamide monotherapy during the study, although four patients showed transient fatigue or somnolence.ConclusionsLacosamide showed good efficacy for controlling seizures with fewer adverse effects, and therefore may be a good candidate as a first-line medication for the treatment of new-onset CECTS.     

Retention rate of pregabalin in drug-resistant epilepsy: 1-year follow-up, single-centre observation in 105 consecutive, adult patients

ObjectivesPregabalin (PGB) is a newer antiepileptic drug (AED) licensed as add-on treatment for partial epilepsy in adults. Efficacy and safety have been proven in several controlled clinical studies. These trials, however, only partially reflect clinical practice. Retention rate has been established as a marker for efficacy and safety of AEDs in long-term follow-up studies.MethodsWe evaluated the data of the first 105 patients treated with PGB at Bethel Epilepsy Centre, a tertiary referral centre for epilepsy. The patients were interviewed after 3, 6 and 12 months.Results105 adult patients (aged 38 ± 13 years) were treated with PGB, on average in combination with 2.1 AEDs (mean observation period 232 days). 76.2% had focal epilepsy, 19.0 multifocal epilepsy, and 3.8% epilepsy with both focal and generalised seizures. 40% continued PGB with the following outcome: 5.7% seizure-free for at least 1 month (4.8% for at least 3 months, 2.4% for at least 6 months; one of the seizure-free patients, however, had had epilepsy surgery during the observational period), 17.1% responders (≥50% reduction of seizure frequency but not seizure-free), 13.3% with unchanged or increased seizure frequency. Reasons for withdrawal were lack of efficacy (47.6%) or side-effects (12.7%).ConclusionsPGB is a new therapeutic option as add-on therapy for patients with highly refractory focal epilepsies although the therapeutic success that can be expected in this group of patients is limited.     

Vigabatrin as first add-on treatment in carbamazepine-resistant epilepsy patients

Numerous clinical reports and several controlled clinical trials have confirmed that vigabatrin is both effective and well-tolerated as an add-on treatment for patients with drug-resistant epilepsy. This report presents the results of a study of 40 patients (22 women and 18 men), aged I960 years (mean 37 years), with partial seizures (with or without secondary generalization) and receiving carbamazepine, 600-1800 mg/day. Vigabatrin was given as first add-on drug at a dose of 2-3 g/day for an average of 6 months, in order to assess the clinical response before considering other anti-epilepsy drugs. There was a significant decrease in seizure frequency, from a median of 13 seizures/month at baseline, to 3 seizures/month during the last month on vigabatrin (p<0.01). Seven patients became seizure-free (17.5%). The most common adverse events experienced during the study were drowsiness, diplopia/blurred vision, and were already present before vigabatrin treatment. In conclusion, vigabatrin is effective as a first add-on therapy for partial epilepsy, refractory to carbamazepine monotherapy, and appears to be a worthy clinical alternative to other drug combinations.     

Rapid loading of intravenous lacosamide: Efficacy and practicability during presurgical video‐EEG monitoring

Purpose: This study investigates immediate efficacy and safety of intravenous application of de novo lacosamide (LCM) as add‐on therapy in patients with pharmacoresistant focal epilepsy. Methods: During presurgical video–electroencephalography (EEG) monitoring, 17 adult inpatients received LCM infusion (200 mg every 12 h for 2–3 days) followed by oral formulation with the same regimen. Before and after intravenous application of LCM, seizures and interictal epileptiform discharges (IEDs) recorded with continuous video‐EEG monitoring were analyzed, and an assessment of adverse events (AEs) was performed daily. To evaluate the midterm tolerability and efficacy, follow‐up visits were conducted 1 and 3 months after discharge from hospital. Key Findings: In the acute phase, intravenous initiation of LCM was well tolerated with few mild or moderate AEs (3 of 17, 17.6%). A significant reduction of seizure frequency in the treatment phase as compared to mean seizure frequency in the 2‐day baseline phase was achieved (p < 0.05 for the first treatment day, and p < 0.005 for the second treatment day). On the first treatment day, 61.5% of the patients were seizure free, and 84.6% on the second treatment day. IED reduction after intravenous application of LCM was not significant. After 1 month, the 50% responder rate was 46.6% and after the 3‐month period, 42.8%. Significance: Our data suggest that rapid intravenous initiation of de novo LCM is safe and may protect against seizures in a rapid and midterm time window.     

Safety and Efficacy of Lacosamide in the Intensive Care Unit

Background  

Seizures are common in critically ill patients and can impact morbidity and mortality. Traditional anti-epileptic drugs (AEDs) in this setting are not always effective and are associated with adverse events and drug interactions. Lacosamide (LCM) is a new AED which is available in parental form although few studies have evaluated the safety and efficacy of LCM in critically ill patients.     

Rufinamide for refractory focal seizures: An open-label,multicenter European study

PurposeThe present study aimed to assess the efficacy and tolerability of rufinamide as adjunctive drug for the treatment of a large series of children, adolescents and adults with refractory cryptogenic or symptomatic focal epilepsy.MethodsPatients were recruited in a prospective, add-on, open-label treatment study from six Italian and one German centers for pediatric and adolescent epilepsy care. Inclusion criteria were: (1) age 3 years or more; (2) diagnosis of cryptogenic or symptomatic focal epilepsy refractory to at least three previous antiepileptic drugs (AEDs), alone or in combination; (3) more than one seizure per month in the last 6 months; (4) use of at least one other AED, but no more than three, at baseline; (5) informed consent from parents and/or caregivers.ResultsSixty-eight patients (40 males, 28 females), aged between 3 and 63 years (mean 19.9 years, median 16.0) ± SD 12.58, with cryptogenic (28 pts, 41.2%) or symptomatic focal epilepsy (40 pts, 58.8%), were recruited in the study. After a mean follow-up period of 10.4 ± 10.29 months, twenty-two patients (32.3%) had a 50–99% seizure reduction, and none became seizure-free. Twelve patients (17.6%) had a 25–49% seizure decrease, while in 30 (44.1%) seizure frequency was unchanged. A seizure worsening was reported in 5 patients (7.3%). A better response to rufinamide occurred in frontal lobe seizures (51.6%) and secondary generalized tonic–clonic seizures (50%).ConclusionRufinamide was effective against focal-onset seizures, particularly in the treatment of secondary generalized frontal lobe seizures.     

Pregabalin as adjunctive therapy for partial epilepsy: An audit study in 96 patients from the South East of England

IntroductionPregabalin (PGB) was licensed in the EU in 2004 as an adjunctive therapy in partial epilepsy. It is also licensed for neuropathic pain and generalised anxiety.AimsTo identify the clinical usefulness and side effects of add-on PGB in out-patient epilepsy clinics.MethodsWe performed an audit on 96 consecutive patients (44 male) prescribed PGB for refractory epilepsy. Mean follow-up, for those who remained on PGB, was 23 months (range 12–39 months).ResultsFifty patients remained on PGB, 37 of whom reported clear improvement in seizure frequency. Among these 37 patients, 1 was seizure free for 15 months; 29 had a seizure reduction of >50%; and 7 improved by <50%. Eight patients reported a decrease in seizure severity without change in seizure frequency. Nine patients reported an incidental improvement in anxiety.Side effects were reported by 25 patients out of the 50 patients still on treatment: 12 reported drowsiness or tiredness, 8 weight gain, 7 dizziness, 2 headache, 2 cognitive side effects, 1 irritability, 1 itchiness, 1 anxiety, and 1 transient rash.Among the 46 patients who discontinued treatment, 9 had worsening of seizure frequency, 27 lack of efficacy and 9 intolerable side effects necessitating withdrawal (4 dizziness or drowsiness, 2 weight gain, 1 peripheral oedema, 1 pain in arms and legs, 1 irritability and cognitive side effects). One patient had a seizure related death (probably drowning) within 1 month of starting PGB.ConclusionPregabalin seems to be an effective and well-tolerated anti-epileptic drug when used as add-on treatment in patients with refractory partial epilepsy.     

Does the seizure frequency increase in Ramadan?

During Ramadan, the ninth month of the Islamic lunar calendar, adult Muslims are required to refrain from taking any food, beverages, or oral drugs, as well as from sexual intercourse between dawn and sunset. In this study, we aimed at discovering alterations in drug regimens and the seizure frequency of epileptic patients during Ramadan (15 October 2004–13 November 2004). In the 3 months following Ramadan in the year 2004, 114 patients with epilepsy who were fasting during Ramadan were examined at our Epilepsy Department. Of the 114 patients who were included in the study, 38 patients had seizures and one of these patients developed status epilepticus during Ramadan. When the seizure frequency of these patients during Ramadan was compared to that in the last 1 year and last 3 months period just prior to Ramadan, a statistically significant increase was observed (p < 0.001). Moreover, there was an important increase in the risk of having seizures in the patients who changed their drug regimens compared with those who did not (p < 0.05). In the patients who received monotherapy or polytherapy, no difference in the frequency of seizures during Ramadan was seen (p > 0.05).During Ramadan, an increase in the seizure frequency of patients with epilepsy was observed. The most important reason for this situation was the alteration in the pharmacokinetics and pharmacodynamics of drugs, and consequently, in their efficacy. We believe that in the patients who received monotherapy and who did not change their drug regimes, the increase in seizure frequency may have been related to the changes in their daily rhythms, emotional stress, tiredness and their day-long fasting.     

Early clinical experience with lacosamide as adjunctive therapy in patients with refractory focal epilepsy and nocturnal seizures

This retrospective study reports the early experience with lacosamide (LCM) as adjunctive therapy in Spanish patients with refractory focal epilepsy. Sixty patients (mean age 38.3 years, 54% women, mean epilepsy duration 27.2 years, mean seizure rate 9.7/month, and 28% with mainly nocturnal seizures) taking ≥2 antiepileptic drugs (mean 2.2) were included. LCM maintenance doses were 200, 300, 400, and 500mg/day in 31, 16, 10, and 3 patients, respectively. Patients were followed up for 13-24 months. Twenty-eight patients (47%) reported a ≥50% reduction in seizure frequency. A ≥50% reduction in seizure frequency was reported by 65% and 40% of patients in the nocturnal seizure and diurnal seizure subgroups, respectively (p>0.05). Of the 28 responders, 2 achieved stable periods of seizure freedom of 6 and 11 months after starting LCM. Twenty patients (33%) reported drug-related adverse events (AEs); the most common was dizziness (16 patients). LCM was withdrawn in 8 patients (13%). There were no serious AEs. These results support the efficacy and safety of adjunctive LCM in patients with partial-onset seizures.