Treatment Of Lennox-Gastaut Syndrome Research Articles

An unfortunate challenge: Ketogenic diet for the treatment of Lennox–Gastaut syndrome in tyrosinemia type 1

The ketogenic diet is an evidence-based treatment for resistant epilepsy including Lennox-Gastaut syndrome. This diet is based on low carbohydrate-high fat intakes. Dietary treatment is also therapeutic for inborn errors of metabolism such as aminoacdiopathies. We report a child with both Lennox-Gastaut syndrome and tyrosinemia type 1. This epilepsy syndrome resulted form a porencephalic cyst secondary to brain abscesses that occurred during the management of malnutrition due to untreated tyrosinemia type 1. We used a ketogenic diet as treatment for Lennox-Gastaut syndrome taking into account dietary requirements for tyrosinemia type 1. The patient was transiently responder during a 6-month period. This report illustrates that ketogenic diet remains a therapeutic option even when additional dietary requirements are needed.

Somnolence and Sedation Were Transient Adverse Events for Most Patients Receiving Clobazam Therapy: Post Hoc Analysis of Trial OV-1012 Data

Background: Somnolence-related adverse events (AEs) are common with benzodiazepine treatment. Clobazam is a uniquely structured 1,5-benzodiazepine indicated in the US for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients ≥ 2 years old. This post hoc analysis of the phase III OV-1012 trial evaluated the incidence, as well as time to onset and resolution, of somnolence and/or sedation AEs following treatment with clobazam for patients with LGS. Methods: OV-1012 was a double-blind, placebo-controlled study that compared three oral dosages of clobazam with placebo as adjunctive therapy in patients 2 - 60 years of age with LGS. Following a 4-week baseline phase, patients who had ≥ 2 drop seizures per week were randomized to placebo or clobazam 0.25, 0.5, or 1.0 mg/kg/day (low-dosage, medium-dosage, and high-dosage, respectively). Treatment included a 3-week titration phase, followed by a 12-week maintenance phase. Incidence, time to onset, duration, and time to resolution of somnolence/sedation AEs were analyzed for patients treated with placebo, or low-, medium-, or high-dosage clobazam. Results: The incidence of somnolence and/or sedation was greater for patients treated with any dosage of clobazam (26%) than placebo (15%), and the incidence increased with greater dosages of clobazam (low-dosage, 17%; medium-dosage, 27%; and high-dosage, 32%). For most patients, onset of these events was within the first 3 weeks of treatment, corresponding to the titration phase. The majority of these events resolved (placebo, 73%; low-dosage, 82%; medium-dosage, 63%; and high-dosage, 83%). The median duration of these somnolence/sedation AEs was 1 month for all clobazam treatment groups. Conclusions: Somnolence and sedation were relatively common AEs observed during clobazam treatment for LGS in OV-1012 and were dosage-related. Most of these events were transient and resolved within a few weeks. J Neurol Res. 2015;5(4-5):252-256 doi: http://dx.doi.org/10.14740/jnr334w

Rufinamide treatment for refractory epilepsy in a largely pediatric population

To determine the safety, tolerability, and efficacy of rufinamide in treating refractory epilepsy in a largely pediatric population. A retrospective chart review was conducted of all patients prescribed rufinamide from December 2008 to July 2010 in the Pediatric Epilepsy Program at Massachusetts General Hospital for Children. Eighty-eight patients on rufinamide with sufficient data for analysis were included in the study. Eight (9.1%) patients had >90% seizure reduction, 40 (45.5%) patients had 50-90% seizure reduction, 19 (21.6%) patients had <50% seizure reduction, and 21 (23.9%) patients had no change in seizure frequency. Generally mild side effects were reported by 28 (31.8%) patients, with the two most common side effects being decreased appetite in seven (8.0%) patients, and somnolence in six (6.8%) patients. Rufinamide appears to be an effective, safe, and well-tolerated antiepileptic drug in the treatment of broad-spectrum intractable epilepsy, expanding outside its specific Food and Drug Administration approved usage in treatment of Lennox-Gastaut syndrome.

RUFINAMIDE IN THE TREATMENT OF LENNOX–GASTAUT SYNDROME: REVIEW OF FOREIGN LITERATURE

Lennox–Gastaut syndrome (LGS) is childhood-onset epileptic encephalopathy characterized by frequent polymorphic seizures, including tonic, axial, obvious cognitive impairments, interictal EEG slow spike-wave discharges with fast activity at 10–20 Hz, which are frequently associated with tonic seizures and resistance to therapy. Treatment for LG presents great challenges due to the fact that its clinical picture is characterized by a concurrence of a few types of seizures and their resistance to drug therapy. In this connection, there are great expectations for the design of new antiepileptic drugs that have radically other mechanisms of action and must aim specially for the treatment of this severe form of epilepsy. The authors review the foreign literature on the use of the new in Russia antiepileptic drug rufinamide (Inovelon) registered just for the treatment of adult patients and in children who are at least 4 years old. Rufinamide (Inovelon) was registered in Russia in January 2015 as adjunctive treatment of seizures associated with LGS in patients from 4 years of age. The paper describes the mechanism of action, pharmacokinetics, efficacy, and tolerability of rufinamide in LGS. Numerous trials have demonstrated the efficacy and good tolerability of rufinamide in the treatment of LGS.

Levetiracetam – epilepsy treatment, pharmacokinetics, mechanism of action, interaction and toxicity

Kozlowski Piotr, Czepinska-Cwik Wioleta, Kozlowska Magdalena, Kozlowska Karolina. Levetiracetam – epilepsy treatment, pharmacokinetics, mechanism of action, interaction and toxicity. Journal of Education, Health and Sport. 2015;5(4):143-150. ISSN 2391-8306. DOI: 10.5281/zenodo.16694 http://ojs.ukw.edu.pl/index.php/johs/article/view/2015%3B5%284%29%3A143-150 https://pbn.nauka.gov.pl/works/553762 http://dx.doi.org/10.5281/zenodo.16694 Formerly Journal of Health Sciences. ISSN 1429-9623 / 2300-665X. Archives 2011 – 2014 http://journal.rsw.edu.pl/index.php/JHS/issue/archive Deklaracja. Specyfika i zawartośc merytoryczna czasopisma nie ulega zmianie. Zgodnie z informacją MNiSW z dnia 2 czerwca 2014 r., ze w roku 2014 nie bedzie przeprowadzana ocena czasopism naukowych; czasopismo o zmienionym tytule otrzymuje tyle samo punktow co na wykazie czasopism naukowych z dnia 31 grudnia 2014 r. The journal has had 5 points in Ministry of Science and Higher Education of Poland parametric evaluation. Part B item 1089. (31.12.2014). © The Author (s) 2015; This article is published with open access at Licensee Open Journal Systems of Kazimierz Wielki University in Bydgoszcz, Poland and Radom University in Radom, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 20.01.2015. Revised 27.03.2015. Accepted: 27.03.2015. LEVETIRACETAM – EPILEPSY TREATMENT, PHARMACOKINETICS, MECHANISM OF ACTION, INTERACTION AND TOXICITY Piotr Kozlowski 1 , Wioleta Czepinska-Cwik 2 , Magdalena Kozlowska 3 , Karolina Kozlowska 4 1 Katedra i Zaklad Anatomii Prawidlowej Czlowieka, UM w Lublinie 2 Klinika Chorob Wewnetrznych, 1 Wojskowy Szpital Kliniczny z Polikliniką w Lublinie 3 Katedra i Zaklad Farmakologii doświadczalnej i Klinicznej, UM w Lublinie 4 Instytut Filologii Angielskiej, KUL Uniwersytet Medyczny w Lublinie ul. W. Chodźki 1, 20-093 Lublin e-mail: piotr7176@gmail.com Abstract Epilepsy is a common chronic neurological disorder that requires a long-term antiepileptic drug therapy. Epilepsy affects approximately 1% of the world’s population, so about 50 million people worldwide have epilepsy. It more likely occurs among children and people over the age of 65. This chronic condition is characterized by recurrent, unprovoked epileptic seizures. Although there are many innovative methods of seizure control, such as neurosurgery, vagal nerve stimulations (VNS) and ketogenic diet, pharmacology is most forceful method of epilepsy treatment. Unfortunately, anticonvulsant drugs are not always effective; the number of non-responding patients is higher than 30% [2,25,29,31]. Levetiracetam (LEV) is one of the newest AEDs, marketed worldwide only since 2000 [29]. This novel antiepileptic drug has a unique and non-standard mechanism of action. The structure of LEV is similar to the prototypical nootropic drug piracetam. Its novel mechanism of action is connected with the synaptic vesicle protein SV2A in the brain. The elimination plasma half-live of LEV is approximately from 6 to 8 hours among adults. About 66% of the drug is excreted unchanged and 27% as inactive hydrolysis product [12]. LEV is mainly removed by the kidneys so that elimination parallels kidney function (renal clearance: 0,6 ml/min/kg) [3,12,32]. LEV was found to be well tolerated and effective in all types of seizures in adults and children [18]. It can be also used in combinations with other AEDs. The drug may also be useful in treatment of Lennox-Gastaut syndrome [9]. This article reviews available published data on LEV in the treatment of adults and children, including information about LEV`s pharmacokinetics, chemistry, mechanism of action, interactions and toxicity. Key words: levetiracetam, antiepileptic drugs, seizures, epilepsy.

Somnolence and Sedation Were Transient Adverse Events for Most Patients Receiving Clobazam Therapy: Post Hoc Analysis of Trial OV-1012 Data

Background: Somnolence-related adverse events (AEs) are common with benzodiazepine treatment. Clobazam is a uniquely structured 1,5-benzodiazepine indicated in the US for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients ≥ 2 years old. This post hoc analysis of the phase III OV-1012 trial evaluated the incidence, as well as time to onset and resolution, of somnolence and/or sedation AEs following treatment with clobazam for patients with LGS. Methods: OV-1012 was a double-blind, placebo-controlled study that compared three oral dosages of clobazam with placebo as adjunctive therapy in patients 2 - 60 years of age with LGS. Following a 4-week baseline phase, patients who had ≥ 2 drop seizures per week were randomized to placebo or clobazam 0.25, 0.5, or 1.0 mg/kg/day (low-dosage, medium-dosage, and high-dosage, respectively). Treatment included a 3-week titration phase, followed by a 12-week maintenance phase. Incidence, time to onset, duration, and time to resolution of somnolence/sedation AEs were analyzed for patients treated with placebo, or low-, medium-, or high-dosage clobazam. Results: The incidence of somnolence and/or sedation was greater for patients treated with any dosage of clobazam (26%) than placebo (15%), and the incidence increased with greater dosages of clobazam (low-dosage, 17%; medium-dosage, 27%; and high-dosage, 32%). For most patients, onset of these events was within the first 3 weeks of treatment, corresponding to the titration phase. The majority of these events resolved (placebo, 73%; low-dosage, 82%; medium-dosage, 63%; and high-dosage, 83%). The median duration of these somnolence/sedation AEs was 1 month for all clobazam treatment groups. Conclusions: Somnolence and sedation were relatively common AEs observed during clobazam treatment for LGS in OV-1012 and were dosage-related. Most of these events were transient and resolved within a few weeks. J Neurol Res. 2015;5(4-5):252-256 doi: http://dx.doi.org/10.14740/jnr334w

Lennox-Gastaut syndrome: impact on the caregivers and families of patients.

Lennox–Gastaut syndrome (LGS) has a major impact on the health-related quality of life (HRQL) of the affected children as well as their caregivers. The primary caregiver in the family is generally the mother, with support from the father and siblings. The burden of care and the effects of the disease on the child necessitate adjustments in virtually all aspects of the lives of their family. These adjustments inevitably affect the physical, emotional, social, and financial health of the whole family. Numerous sources of support for families can help to ease the burden of care. Improvements in the treatment of LGS, in addition to helping the child with LGS, would likely help improve the HRQL of the family members. This pilot parent survey was designed to explore the impact of epilepsy on caregiver HRQL. Parents of children with epilepsy who had contacted the Epilepsy Information Service at the Wake Forest University School of Medicine, Winston-Salem, NC, USA, were sent questionnaires comprising open- and closed-ended questions. A total of 200 surveys were distributed, with a return rate of 48%. The results revealed that 74% of the parents believed that having a child with epilepsy brought them and their partner closer together. However, when the parents were asked to explain the manner in which epilepsy affected their families, answers included continuous stress, major financial distress, and lack of time to spend with other children. Information and resources for the families of children with LGS could help improve the HRQL of both the patients and their relatives.

The efficacy and tolerability of pharmacologic treatment options for Lennox-Gastaut syndrome.

Lennox-Gastaut syndrome (LGS) is a severe epileptic encephalopathy that appears in childhood. LGS is characterized by a slow spike-wave pattern on electroencephalogram (EEG), cognitive impairment, and multiple seizure types. This mixture of seizure types, along with the need to use more than one type of medication, makes LGS one of the most complicated epilepsies to treat successfully. Recent developments in approved therapies for the treatment of LGS offer physicians more options, but also make developing a treatment strategy that minimizes adverse events more challenging. There are currently 5 treatment options for LGS: felbamate, lamotrigine, topiramate, rufinamide, and clobazam, and several others that are used off-label, each of which has benefits and limitations. There are several factors that must be considered when determining which medication to use when treating patients with LGS, including efficacy, which is assessed by seizure frequency, tolerability, and the anticipated duration of treatment. In this article, data supporting current treatment options are discussed, and important considerations about the treatment of LGS are reviewed.

Surgical options for patients with Lennox‐Gastaut syndrome

Despite ongoing investigation into pharmacologic treatments for Lennox-Gastaut syndrome (LGS), outcomes for chronic administration of medications remain disappointing. In many instances LGS is treatment refractory, resulting in poor prognoses that include intellectual disability, persisting seizures, and psychiatric conditions. For patients with treatment resistance to other modalities for LGS, a further option is surgical intervention. Evaluation for surgery should involve interictal electroencephalogram (EEG), magnetic resonance imaging (MRI) analysis, and age-appropriate neuropsychological/developmental assessment. Resective surgery, where seizure foci are removed, successfully controls seizures in many cases, particularly where lesionectomy or lobar resections are appropriate. Recent studies of resective surgery on individuals with LGS show promising results, with a high percentage of patients having improved seizure control. Corpus callosotomy is a palliative surgical approach that aims at controlling potentially injurious seizures, for example, atonic or drop seizures, by preventing the bilateral spread of epileptic activity. Once associated with a high risk for morbidity and mortality, microsurgical techniques and surgery limited to the anterior region of the callosum have greatly diminished complications of corpus callosotomy surgery. Vagus nerve stimulation, another palliative procedure, offers rates of seizure improvement similar to those of corpus callosotomy, with the exception of atonic seizure for which corpus callosotomy may lead to a greater reduction. Recent advances in surgical techniques offer encouraging options for treatment of LGS.

Current role of rufinamide in the treatment of childhood epilepsy: Literature review and treatment guidelines

PurposeThe literature on the efficacy and safety of rufinamide in childhood-onset epilepsy syndromes currently includes approximately 600 paediatric patients. This paper summarizes the views of a panel of experienced European epileptologists with regard to the current role of rufinamide in the treatment of childhood epilepsies. ResultsRufinamide is effective in decreasing the seizure frequency in the Lennox-Gastaut syndrome (LGS), especially tonic and atonic seizures. It might consequently be preferred to other drugs as a second-line treatment for LGS when drop-attacks are frequent. The mean responder rate in the published studies is 38% with seizure freedom achieved in 2.4% of patients. Rufinamide has shown some efficacy in epileptic encephalopathies other than LGS. It can be also effective as adjunctive therapy in children and adolescents with drug-resistant partial seizures. The available data suggest that rufinamide has an acceptable risk/benefit ratio with quite a low risk of aggravating seizures. Common adverse effects (somnolence, nausea and vomiting) are usually mild and self-limiting; they are more frequently observed during titration than in the maintenance phase, suggesting that low escalation rates might be associated with fewer adverse effects. Rufinamide appears to have a favourable cognitive profile compared with other antiepileptic drugs. ConclusionRufinamide is only approved for adjunctive treatment of seizures associated with LGS in children 4 years of age and older. There are very few data on rufinamide treatment at the onset of LGS or early in the course of the disorder; whether early treatment will improve outcome has yet to be determined.

Treatment of Lennox-Gastaut syndrome

The Lennox-Gastaut syndrome (LGS) is an age-specific disorder, characterised by epileptic seizures, a characteristic electroencephalogram (EEG), psychomotor delay and behavioural disorder. It occurs more frequently in males and onset is usually before the age of eight years, with a peak between three and five years of age. Late cases occurring in adolescence and early adulthood have rarely been reported. Language is frequently affected, with both slowness in ideation and expression in addition to difficulties of motor dysfunction. Severe behavioural disorders (e.g. hyperactivity, aggressiveness and autistic tendencies) and personality disorders are nearly always present. There is also a tendency for psychosis to develop with time. The long-term prognosis is poor; although the epilepsy often improves, complete seizure freedom is rare and conversely the mental and psychiatric disorders tend to worsen with time. To compare the effects of pharmaceutical therapies used to treat LGS in terms of control of seizures and adverse effects. Many people who suffer from this syndrome will already be receiving other antiepileptic medications at the time of their entry into a trial. However, for the purpose of this review we will only consider the effect of the single therapeutic agent being trialled (often as add-on therapy). We searched the Cochrane Epilepsy Group's Specialized Register (18 October 2012), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library Issue 10 of 12, 2012) and MEDLINE (1946 to October week 2, 2012). We also searched EMBASE (1980 to March 2003). We imposed no language restrictions. We searched the International Standard Randomised Controlled Trial Number (ISRCTN) register (18 October 2012) for ongoing trials and in addition, we contacted pharmaceutical companies and colleagues in the field to seek any unpublished or ongoing studies. All randomised controlled trials (RCTs) of the administration of drug therapy to patients with LGS. Two review authors independently extracted data. Analysis included assessing study quality, as well as statistical analysis of the effects on overall seizure rates and effects on specific seizure types (e.g. drop attacks), adverse effects and mortality. We found nine RCTs, but were unable to perform any meta-analysis, because each trial looked at different populations, different therapies and considered different outcomes. The optimum treatment for LGS remains uncertain and no study to date has shown any one drug to be highly efficacious; rufinamide, lamotrigine, topiramate and felbamate may be helpful as add-on therapy, clobazam may be helpful for drop seizures. Until further research has been undertaken, clinicians will need to continue to consider each patient individually, taking into account the potential benefit of each therapy weighed against the risk of adverse effects.

Lennox-Gastaut Syndrome: An Update on Treatment

Lennox-Gastaut syndrome (LGS) is a severe epileptic encephalopathy. Few current treatment options are effective in improving seizure control. This paper reviews the available treatments of LGS and discusses a new option in Canada, rufinamide. It is a wide spectrum anticonvulsant, approved in a number of countries for the treatment of LGS. In a randomized controlled trial in the LGS population, adjunctive rufinamide therapy has been shown to offer significantly greater reduction in total seizure frequency and tonic-atonic seizure frequency in comparison to placebo. Efficacy has been assessed over three years and appears to be sustained. Most adverse events were cognitive (e.g. somnolence) or gastrointestinal in nature and in many cases transient or mild. based on the efficacy and safety data on rufinamide obtained to date, this medication will provide additional benefits to patients with LGS in Canada and is an important consideration for our patients in the adjunctive treatment setting.

Dramatic weight loss with rufinamide

Rufinamide (RUF) is a novel antiepileptic drug considered as second-line therapy in the treatment of Lennox-Gastaut syndrome. Treatment-emergent adverse events (AEs) have consisted mainly of drowsiness, irritability, vomiting, and loss of appetite. RUF is considered as a "weight-neutral" drug. We found clinically significant weight loss in 7 of 15 consecutive adult patients (47%; 3 male, 4 female, aged 18-31 years) treated with RUF as add-on therapy (800-2,400 mg/day: 23.5-57.1 mg/kg/day). The body mass index (BMI) decreased by 7.3-18.7%. Two patients were obese class I before RUF. Five patients (71%) were underweight before RUF (mild in one case, moderate in two cases, and severe in two cases). Four of these patients stopped RUF because of this adverse effect. RUF was recommenced in two patients using a lower and slower dosing strategy; one patient showed improvement in seizure control and no weight loss but RUF was re-stopped in the second patient because of continued weight loss. Despite of weight loss, RUF was continued in two other patients because it reduced seizure activity. We primarily related weight loss to reduced food intake, that is, loss of appetite and nausea, although in two patients no obvious loss of appetite was reported. RUF can cause clinically significant weight loss in adult patients, even at low dose. This AE can affect patients who are already underweight. There is a possibility that lower starting doses and slower escalation might minimize weight loss, but further information is required to determine whether this is the case.

Clobazam for patients with Lennox–Gastaut syndrome and epilepsy

Lennox–Gastaut syndrome (LGS) is a form of childhood epileptic encephalopathy that continues to be challenging to treat and manage. The available treatments have failed to provide good control for patients with this devastating epilepsy syndrome. Clobazam is a promising antiepileptic medication, given its effectiveness and relatively low rates of adverse effects. It has been studied and used in several countries for the treatment of refractory seizures, including those that occur with LGS. Clobazam (Onfi™; Lundbeck Inc., IL, USA) has been studied in the USA to demonstrate its efficacy and safety for the treatment of seizures associated with LGS, and Phase II and III trials have recently been completed. This article will explore the use of clobazam in the treatment of LGS and present the results of Phase II and III studies, along with an overall summary of the treatment of LGS, as well as the possible role of clobazam in a treatment algorithm. We based this article on the most relevant reports with the term ‘clobazam’ found through a Medline search (1966–2011).

The ketogenic diet in the treatment of Lennox-Gastaut syndrome

The ketogenic diet in the treatment of Lennox-Gastaut syndrome

Efficacy of the ketogenic diet in Lennox–Gastaut syndrome: a retrospective review of one institution’s experience and summary of the literature

To determine the efficacy of the ketogenic diet for children with Lennox-Gastaut syndrome (LGS) at our institution and in the literature. The records of children with LGS initiated on the ketogenic diet at our institution from 1994 to 2010 were reviewed. Inclusion criteria included the presence of ≤2.5Hz spike-and-wave complexes on electroencephalogram, multiple seizure types including tonic, atonic, or atypical absence, developmental delay, and age under 1 year. We additionally reviewed the literature for cases of LGS treated with the ketogenic diet and their outcomes. Seventy-one children (41 males, 30 females, median age 3y 6mo, range 18mo-18y), with LGS were initiated on the ketogenic diet. Using an intent-to-treat analysis, after 6 months, 36 (51%) achieved more than 50% seizure reduction, 16 (23%) experienced more than 90% seizure reduction, and 1 (1%) achieved seizure freedom. Results were similar after 12 months. Age, sex, side effects, valproate use, and history of infantile spasms were not predictive of more than 90% seizure reduction. In the literature, 88 of 189 (47%) children with LGS had more than 50% seizure reduction after 3 to 36 months of ketogenic diet treatment. The ketogenic diet is efficacious in the treatment of LGS, with approximately one-half of children responding at 12 months.

Erratum to: The cost effectiveness of rufinamide in the treatment of Lennox-Gastaut syndrome in the UK

Erratum to: The cost effectiveness of rufinamide in the treatment of Lennox-Gastaut syndrome in the UK

Rufinamide from clinical trials to clinical practice in the United States and Europe

Rufinamide is a triazole derivative structurally unrelated to other antiepileptic drugs that is indicated for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients aged ≥4 years. Originally granted orphan drug status, marketing authorisation was obtained on the basis of a randomised, double-blind, placebo-controlled trial conducted in 138 LGS patients. An open-label extension study subsequently demonstrated that rufinamide's efficacy and tolerability were maintained over the longer term (median duration of treatment, 432 days). Recently published reports from Europe and the United States have described the use of adjunctive rufinamide to treat LGS in clinical practice. These data complement the clinical trial results, by providing information on the efficacy and tolerability of rufinamide when used on an individualised basis in real-world practice, under less tightly restricted conditions in terms of patient population and dosing strategies. A comparison of the data reveals that a "lower and slower" dosing strategy tends to be adopted in clinical practice, in comparison with the clinical trial, which does not appear to compromise efficacy, but may provide improvements in tolerability. Individual case reports provide additional valuable information on how rufinamide is being used to treat different seizure types associated with LGS. Since clinical experience with rufinamide is currently at an early stage, there are still unanswered questions relating to its use, and it is likely that its place in the adjunctive treatment of LGS will evolve as further data emerge.

Update on rufinamide in childhood epilepsy

Rufinamide is an orally active, structurally novel compound (1-[(2,6-difluorophenil1) methyl1]-1 hydro 1,2,3-triazole-4 carboxamide), which is structurally distinct from other anticonvulsant drugs. It was granted orphan drug status for the adjunctive treatment of Lennox-Gastaut syndrome (LGS) in the United States in 2004, and released for use in Europe in 2007. In January 2009, rufinamide was approved by the United States Food and Drug Administration for treatment of LGS in children 4 years of age and older. It is also approved for adjunctive treatment for partial seizures in adults and adolescents. Rufinamide’s efficacy mainly against atonic/tonic seizures in patients with LGS seems nowadays indubitable and has been confirmed both in randomized controlled trial and in open label extension studies. More recently, rufinamide was evaluated for the adjunctive treatment of childhood-onset epileptic encephalopathies and epileptic syndromes other than LGS, including epileptic spasms, multifocal epileptic encephalopathy with spasm/tonic seizures, myoclonic-astatic epilepsy, Dravet syndrome and malignant migrating partial seizures in infancy. This review updates the existing literature data on the efficacy and safety/tolerability of rufinamide in childhood-onset epilepsy syndromes.

The Cost Effectiveness of Rufinamide in the Treatment of Lennox-Gastaut Syndrome in the UK

Lennox-Gastaut syndrome (LGS) is a catastrophic childhood form of epilepsy. The syndrome is characterized by mental impairment, frequent seizures of multiple types that are particularly resistant to treatment, and high rates of seizure-related injury. With the introduction of newer, but more costly, antiepileptic drugs (AEDs), it is important that decision makers are able to assess their value in the management of this rare and difficult-to-treat condition. To evaluate the cost effectiveness, from the UK NHS perspective, of rufinamide in patients with LGS. An individual patient-simulation model was developed to estimate the total treatment-related costs and clinical benefits of rufinamide compared with topiramate and lamotrigine over a 3-year time horizon. The model examines the treatment scenarios of adding rufinamide, lamotrigine or topiramate to older AEDs (standard therapy), or standard therapy alone within a primary-care or community setting. Three placebo-controlled clinical trials of adjunctive AED treatment for children with LGS were analysed. There are no head-to-head comparator studies. Between 98 and 139 patients were randomized in each study and the mean age in each study was 10, 11 and 14 years. A mixed-treatment comparison using a random-effects model was carried out on the number of patients in each response category, using the placebo arms of the respective trials. The primary outcome measure was the percentage of successfully treated patients, defined as >50% reduction in the frequency of total seizures and drop attacks. The hypothesis being tested was formulated after data collection. Costs ( pound, year 2006/07 values) of patient monitoring, switching treatments, hospitalization due to seizure, treatment of adverse effects, and personal and social services were included in the analysis. Results of 10,000 Monte Carlo simulations were bootstrapped to conduct probabilistic sensitivity analysis. Over 3 years, adjunctive rufinamide resulted in higher total costs than topiramate and lamotrigine; however, with more patients being treated successfully, this leads to acceptable incremental cost-effectiveness ratios. If society is prepared to pay at least 250 pounds for a 1% increase in the number of successfully treated LGS patients, in terms of a 50% reduction in the frequency of drop attacks, the probability of the treatment with rufinamide being cost effective is >80%. This cost-effectiveness analysis suggests that rufinamide results in more LGS patients being treated successfully at a reasonable cost from a UK NHS perspective.