Levetiracetam monotherapy for adults with localization-related epilepsy

We identified 37 patients with a history of partial seizures, with and without secondarily generalization, who received levetiracetam (LEV) (Keppra) monotherapy. Patients began LEV either as first line therapy (n=9) or were converted to LEV monotherapy (n=28) after failing prior antiepileptic medications (AEDs). Thirty-four patients continued on LEV for at least six months; of these, 13 patients became seizure free and 15 patients had >50% reduction in their seizures. Three patients discontinued LEV because of adverse effects. LEV monotherapy can be effective and well tolerated in adults with new onset and difficult-to-control partial epilepsy. A prospective, large, double blind monotherapy study is needed to confirm this finding.     

Vagus nerve stimulation for drug-resistant epilepsy in children and young adults

We present our experience with the use of intermittent vagal nerve stimulation in 13 patients with medically intractable epilepsy. A surgical approach, with the exception of callosotomy, was impossible. The age range was 6-28 years (median 17 years). In all patients the epilepsy was severe and in six of them was symptomatic. Seven patients had Lennox-Gastaut syndrome, one epilepsy with myoclonic-astatic seizures, four localization-related and one symptomatic generalized epilepsy. The length of the follow-up averaged 22 months (range 8 months-3 years). Of the 13 patients, five (38.4%) had a 50% or more reduction in the number of seizures compared with preimplantation. Of these patients, one with a localization-related epilepsy had a 90% reduction as well as a significant improvement in alertness. Three patients showed no improvement with regard to the number of seizures but there was an improvement in alertness and, in one case in hyperactivity. Some seizure types responded better than others did: complex partial seizures with secondary generalization and atonic seizures. All our responsive patients improved in the first 2 months of VNS activation and only one case with further improvement was observed after this period. Considering the severity of the epilepsy the results can be considered satisfactory. We think that this treatment appears to be a safe adjunctive therapy for children and adults with medically and surgically intractable epilepsy.     

Hormone profiles in young adults with epilepsy treated with sodium valproate or lamotrigine monotherapy

PURPOSE: Treatment with sodium valproate (VPA) may be associated with polycystic ovarian syndrome (PCOS) in some women with epilepsy. By comparing hormone profiles in young adults taking VPA or lamotrigine (LTG) as monotherapy, this study aimed to explore whether a pharmacologic effect of VPA could be responsible for this observation. METHODS: Hormone profiles in men and women taking VPA (n = 40) or LTG (n = 36) monotherapy for epilepsy were compared. None of the women were receiving hormonal contraception or replacement. Patients gave details of seizure type and frequency, menstrual cycle, and medical and drug history. Body mass index was calculated, and fasting insulin, glucose, cholesterol, triglycerides (TG), high- and low-density lipoproteins, testosterone, dihydroepiandosterone (DHEA), androstenedione, sex hormone-binding globulin (SHBG), free androgen index (FAI), luteinising hormone (LH), follicle-stimulating hormone (FSH), and antiepileptic drug (AED) concentrations were measured. RESULTS: There were no differences between treatment groups for both sexes in age and seizure control. Only four obese VPA-treated women were hyperinsulinaemic (p = 0.05); three with abnormal menstrual cycles; one with raised testosterone. Testosterone (p = 0.02), FAI (p = 0.03), and TG (p = 0.02) levels were higher, however, in women taking the drug. Obese patients of both sexes (p = 0.01) and VPA-treated men (p = 0.03) had higher insulin concentrations. CONCLUSIONS: VPA therapy may be associated with subclinical elevation in fasting insulin levels. Testosterone and TG levels were higher in VPA-treated women compared with the levels in those taking LTG. However, only a minority of obese females exhibited biochemical characteristics suggestive of PCOS. Biochemical screening may allow women at risk of developing PCOS to avoid VPA.     

Levetiracetam monotherapy in children with epilepsy

Although levetiracetam has shown efficacy in children with epilepsy, when used as adjunctive therapy, limited data are available regarding its use as monotherapy. The objective of this study is to evaluate the efficacy and tolerability of levetiracetam monotherapy in a cohort of pediatric patients with epilepsy. A retrospective analysis of pediatric epilepsy patients receiving levetiracetam at a single institution was performed over a 3-year period. Eighty-one patients were identified, 18 of whom received levetiracetam as monotherapy (mean age, 9.6 years). Epilepsy types were partial in 14 and generalized in 4. Conversion to levetiracetam monotherapy occurred in 16 patients due to lack of efficacy or adverse events, and 2 patients were initially started on monotherapy. Dose range of levetiracetam was 14-60 mg/kg, and duration of therapy ranged from 2-24 months. Eleven patients became seizure free on levetiracetam, one had at least 50% reduction in seizures, and six others had no change in seizure frequency. Adverse events included worsening of behavior, irritability, and possible cognitive changes, seen in 4 patients. Levetiracetam was discontinued in seven patients overall. Levetiracetam monotherapy appeared to be effective and well tolerated in this group of children with epilepsy and warrants further investigation in a well-controlled, prospective study.     

Effect of antiepileptic drug monotherapy on urinary pH in children and young adults

Objects Since alkaline urine is a risk factor for urolithiasis, the relationship between antiepileptic drugs and urinary pH was retrospectively studied in epilepsy patients treated with antiepileptic drug monotherapy for more than 1 month.Methods A total of 913 urinary samples from antiepileptic drug-treated patients were compared with 780 age-matched control samples, and with 112 samples from epilepsy patients who had not been treated with antiepileptic drugs. The antiepileptic drugs administered were carbamazepine, valproate, phenobarbital, zonisamide, sulthiame, and phenytoin.Conclusions The proportion of the acid urine in the valproate-treated patients was lower than that in controls. The proportion of the alkaline urine in the valproate-treated patients was higher than that in controls. This effect was independent of age, sex, and the serum valproate concentration. There was no significant difference in urinary pH among the epilepsy patients treated with other antiepileptic drugs, the epilepsy patients who had not been treated with antiepileptic drugs, and the controls.     

Zonisamide for the treatment of epilepsy

The availability of new antiepileptic drugs with different mechanisms of action has widened our therapeutic choice, allowing better tailoring of treatment regimens to address specific needs. Zonisamide is the latest addition to the pharmacological management of epilepsy in Europe, following extensive clinical experience in Japan and the USA. This article reviews the structure, mechanism of action, pharmacokinetics and drug interactions of zonisamide. The four double-blind, placebo-controlled trials in patients with drug-resistant focal seizures are also presented. They complement pre- and postmarketing studies conducted in Japan and provide clear-cut evidence that the drug has efficacy as an add-on treatment in this indication. Reports on zonisamide monotherapy and on the use of the drug for the control of several types of seizures (typical and atypical absences, tonic and myoclonic) and syndromes in children and adults are also commented on. These were all open-label studies, as is often the case with other antiepileptic drugs, dealing with treatment of epilepsy in children. The Japanese, US and European data provide a large database of safety information suggesting that the drug is well tolerated with mild-to-moderate adverse events (e.g., somnolence and dizziness). Nephrolithiasis appears to have a very low incidence and cutaneous reactions are rare. The available data provide an excellent foundation on which clinicians can build their knowledge on this drug, although the broad-spectrum efficacy of zonisamide needs to be confirmed through randomized trials.     

Zonisamide monotherapy in a multi-group clinic.

OBJECTIVE: Reports on zonisamide monotherapy are limited despite favourable preliminary data, and typically restricted to tertiary referral centres. The goal of this study is to report clinical experience with zonisamide monotherapy in a large, multi-group clinic setting. METHODS: We reviewed the charts of patients treated with zonisamide monotherapy in the Neurology Department of the Kelsey-Seybold Clinic (Houston, Texas) during an 18-month period. We analysed subgroups of patients who were naive to antiepileptic drug (AED) therapy (Group 1) and those who had previous exposure to AEDs (Group 2). RESULTS: The study included 54 paediatric and adult patients with a variety of seizure types: 15 patients in Group 1 and 39 patients in Group 2. Mean maintenance zonisamide dosages in the two groups were similar (193 mg/day in Group 1 vs. 218 mg/day in Group 2). Thirty-eight patients (70.4%) continued zonisamide monotherapy, with 7 patients (13.0%) adding a second AED and 9 patients (16.7%) switching to a different drug. Of the 24 patients who became seizure free on zonisamide monotherapy, 11 were on the 100-mg initial dosage. Zonisamide monotherapy was well tolerated. CONCLUSIONS: Zonisamide monotherapy is safe and effective for a variety of seizure types and may be appropriate as first-line therapy in some cases.     

Bone mineral density in children, adolescents, and young adults with epilepsy

Purpose:   The aim of this study was to assess bone mineral density (BMD) in a large population of children, adolescents, and young adults with epilepsy alone or in association with cerebral palsy and/or mental retardation.
Methods:   Ninety-six patients were enrolled in the study. The group comprised 50 males and 46 females, aged between 3 and 25 years (mean age 11 years). The control group consisted of 63 healthy children and adolescents (23 males, 40 females), aged between 3 and 25 years (mean age 12.1 years). Patients underwent a dual-energy x-ray absorptiometry (DEXA) scan of the lumbar spine (L1–L4) and the z scores were calculated for each patient; the t score was considered for patients 18 years of age or older.
Results:   Abnormal BMD was found in 56 patients (58.3%), with values documenting osteopenia in 42 (75%) and osteoporosis in 14 (25%). A significant difference emerged between epileptic patients and the control group in BMD, z score, and body mass index (BMI) (p = <0.001). Lack of autonomous gait, severe mental retardation, long duration of antiepileptic treatment, topiramate adjunctive therapy, and less physical activity significantly correlated with abnormal BMD.
Discussion:   This study detected abnormal BMD in more than half of a large pediatric population with epilepsy with or without cerebral palsy and/or mental retardation. The clinical significance of these findings has yet to be clarified.     

Topiramate monotherapy in newly diagnosed epilepsy in children and adolescents

A double-blind, dose-controlled study evaluated topiramate as monotherapy in 470 patients with newly diagnosed (< or = 3 months) epilepsy or epilepsy relapse in the absence of therapy. In addition to having at least 2 lifetime-unprovoked seizures, patients had 1 or 2 partial-onset seizures or generalized-onset tonic-clonic seizures during a 3-month retrospective baseline. The trial included a large cohort (N = 151, 32%) of children and adolescents 6 to 15 years of age. Eligible patients were randomized to treatment groups in which topiramate was titrated to target maintenance dosages of either 400 mg/day (n = 77) or 50 mg/day (n = 74). Patients were followed for at least 6 months. Based on Kaplan-Meier analyses, the primary efficacy endpoint of time to first seizure favored the higher topiramate dose in both the overall population and the cohort of children/adolescents. The probability that children/adolescents remaining in the study were seizure free at 6 months was 78% in the 50-mg target dose group and 90% with the higher dose. At 12 months, the probability of being seizure free was 62% and 85%, respectively. The incidence of treatment-limiting adverse events was 4% in the 50-mg target dose group and 14% in the group assigned to 400 mg as a target dose. The most common adverse events, excluding typical childhood illnesses, were headache, appetite decrease, weight loss, somnolence, dizziness, concentration/attention difficulty, and paresthesia. As shown in this subset analysis, topiramate is effective and well tolerated as monotherapy in children and adolescents.     

左乙拉西坦单药治疗小儿癫痫的自身对照研究

目的研究左乙拉西坦作为单药治疗不同类型癫痫患儿的临床疗效和安全性。方法采用前瞻性研究,对62例不同类型癫痫患儿进行左乙拉西坦单药治疗。左乙拉西坦起始剂量为20 mg/(kg.d),分两次服用,每两周增加10 mg/(kg.d),维持剂量30～40 mg/(kg.d)。稳定期:维持加量期12周,每个月观察1次,以治疗前3个月的发病频率为基础,完成了6个月的观察期,随访6～24个月(平均随访12.8个月),观察发作频率的变化及不良反应。结果 62例入选患儿,完全控制发作38例,占61.3%,显效8例,占12.9%;有效9例,占14.5%;无效4例,占6.5%;加重3例,占4.8%。总有效率为88.7%,两年治疗保留率为72%。左乙拉西坦治疗前后发作频率改变有统计学意义(P0.005)。结论左乙拉西坦作为单药治疗小儿各型癫痫有良好疗效及安全性。     

Social stigma for adults and children with epilepsy

Summary   For many people with epilepsy, the continuing social reality of their condition is as a stigma. Epilepsy stigma has three different levels; internalized, interpersonal, and institutional. While there have been documented improvements in public attitudes towards epilepsy, the remnants of "old" ideas about epilepsy continue to inform popular concepts resulting in a difficult social environment for those affected. The social and quality of life problems arising from a diagnosis of epilepsy can represent greater challenges than are warranted by its clinical severity. The relationship between stigma and impaired quality of life is well documented. Tackling the problem of stigma effectively requires that all three of different levels at which it operates are systematically addressed.     

Clinical characteristics of children and young adults with co-occurring autism spectrum disorder and epilepsy

The association between autism spectrum disorder (ASD) and epilepsy has been described for decades, and yet we still lack the full understanding of this relationship both clinically and at the pathophysiologic level. This review evaluates the available data in the literature pertaining to the clinical characteristics of patients with autism spectrum disorder who develop epilepsy and, conversely, patients with epilepsy who develop autism spectrum disorder.Many studies demonstrate an increased risk of epilepsy in individuals with ASD, but rates vary widely. This variability is likely secondary to the different study methods employed, including the study population and definitions of the disorders. Established risk factors for an increased risk of epilepsy in patients with ASD include intellectual disability and female gender. There is some evidence of an increased risk of epilepsy associated with other factors such as ASD etiology (syndromic), severity of autistic features, developmental regression, and family history. No one epilepsy syndrome or seizure type has been associated, although focal or localization-related seizures are often reported. The age at seizure onset can vary from infancy to adulthood with some evidence of a bimodal age distribution. The severity and intractability of epilepsy in populations with ASD have not been well studied, and there is very little investigation of the role that epilepsy plays in the autism behavioral phenotype. There is evidence of abnormal EEGs (especially epileptiform abnormalities) in children with ASD even in the absence of clinical seizures, but very little is known about this phenomenon and what it means.The development of autism spectrum disorder in patients with epilepsy is less well studied, but there is evidence that the ASD risk is greater in those with epilepsy than in the general population. One of the risk factors is intellectual disability, and there is some evidence that the presence of a particular seizure type, infantile spasms, may increase risk, but some of the data are conflicting.We believe that one of the reasons that so little is known about this phenomenon is the lack of cross talk between researchers and clinicians alike in the two fields. We conclude that large systematic studies that employ strict ascertainment of samples using standardized definitions of both disorders, validated data collection tools, and appropriate longitudinal follow-up are needed to better shed light on certain clinical aspects of the comorbidity of ASD and epilepsy. Ideally, we could provide the optimal diagnostic and treatment services to these patients in a multidisciplinary setting with both epilepsy and neurobehavioral specialists.This article is part of a Special Issue entitled “Autism and Epilepsy”.     

Clonazepam monotherapy for epilepsy in childhood

Sixty patients (age-range one month to 14 years) with other types of epilepsy than infantile spasms were treated with clonazepam. Disappearance of seizures and normalization of abnormal EEG with disappearance of seizures were recognized in 77% and 50%, respectively. Seizures disappeared in 71% of the patients with generalized seizures and 89% of partial seizures. Improvement of abnormal EEG was noticed in 76% of diffuse paroxysms and in 67% of focal paroxysms. In excellent cases, mean effective dosages were 0.086 +/- 0.021 mg/kg/day in infants and 0.057 +/- 0.022 mg/kg/day in schoolchildren, this difference was statistically significant (p less than 0.005). The incidence of side effects such as drowsiness and ataxia was only 5%.     

Stroke in young adults and children

Data from studies of 337 children and 1606 young adults are summarized to identify the major causes of stroke in these age groups. In children under 15 years of age, stroke occurs in patients with congenital heart disease, nonatherosclerotic vasculopathies, infection, and hematologic defects like sickle cell disease. In patients 15 to 35 years of age, dissection, cardioembolism, nonatheroslerotic vasculopathies, and prothrombotic states cause a significant percentage of strokes. In adults over 35 years of age, traditional atherosclerotic risk factors predominate. Lifestyle choices (eg, cigarette smoking, alcohol consumption, and illicit drug use) can significantly increase the rate of stroke among young adults in a community. Limited access to healthcare may increase the role of infectious disease and peripartum complications.     

Outcomes of epilepsy surgery in adults and children

Surgery is widely accepted as an effective therapy for selected individuals with medically refractory epilepsy. Numerous studies in the past 20 years have reported seizure freedom for at least 1 year in 53-84% of patients after anteromesial temporal lobe resections for mesial temporal lobe sclerosis, in 66-100% of patients with dual pathology, in 36-76% of patients with localised neocortical epilepsy, and in 43-79% of patients after hemispherectomies. Reported rates for non-resective surgery have been less impressive in terms of seizure freedom; however, the benefit is more apparent when reported in terms of significant seizure reductions. In this Review, we consider the outcomes of surgery in adults and children with epilepsy and review studies of neurological and cognitive sequelae, psychiatric and behavioural outcomes, and overall health-related quality of life.     

托吡酯单用及添加治疗癫痫302例临床分析

目的　观察托吡酯添加和单药治疗癫痫的临床疗效及不良反应 ,并探讨单药治疗的理想给药模式。方法　入组患者分为 3组 ,A组 10 2例采用托吡酯添加治疗 ,B组 2 0 0例采用托吡酯单药治疗 ,按初始剂量及加量速度不同 B组又分为 B1组、B2组。B1组 10 5例 ,妥泰初始剂量 2 5 mg/ d,增量 2 5 m g/ w至 2 0 0 m g/ d;B2组 95例 ,妥泰初始剂量 5 0 mg/ d,增量 5 0 m g/ w至 2 0 0 m g/ d。维持治疗 12周。记录发作情况及不良反应。结果　 A组总有效率及控制率分别为 6 0 .8%、2 4 .5 % ,B组总有效率及控制率为 76 .8%、4 1.5 % ,两组疗效差异有显著性意义 (P<0 .0 5 )。 B1组总有效率及控制率分别为 77.9%、4 1.9% ,B2组总有效率及控制率分别为 75 .8%、4 0 .0 % ,两组疗效差异无显著性意义 (P>0 .0 5 )。托吡酯对各型部分性发作及强直 -阵挛性发作的疗效差异无显著性意义 (P>0 .0 5 )。B2组不良反应高于 B1组 ,差异有显著性意义 (P<0 .0 5 )。结论　托吡酯添加及单药治疗癫痫具有良好的疗效 ,对发作频率较低的患者宜选用小剂量起始缓慢加量的治疗方法 ,对发作频率较高的患者可考虑予较大起始剂量并以较快速度加量以尽快控制发作