Idiopathic generalised epilepsies: not only for the paediatrician.
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Adolescent↗
Biomedical subjects
J W Sander
Publications and source records attributed to J W Sander.
Levetiracetam: a new therapeutic option for refractory epilepsy.
Levetiracetam (LEV) is the most recently licensed antiepileptic drug (AED) for adjunctive therapy of partial seizures. Its mechanism of action is uncertain but it exhibits a unique profile of anticonvulsant activity in models of chronic epilepsy. Three randomised, double-blind, placebo-controlled trials enrolling 904 patients with refractory partial epilepsy have demonstrated the efficacy of LEV as adjunctive therapy, with a responder rate (> or = 50% reduction in seizure frequency) of 28-41%. Long-term efficacy studies suggest retention rates of 60% after one year, with 13% of patients seizure-free for six months of the study and 8% seizure-free for one year. Adverse effects of LEV, including somnolence, lethargy and dizziness, were generally mild and the frequency of incidents was not significantly different between the active treatment and placebo groups in clinical trials. LEV has no clinically significant pharmacokinetic interactions (PKI) with other AEDs, or with commonly prescribed medications. Preliminary data suggest that LEV has efficacy in primary generalised epilepsy and further randomised trials are under way. The combination of potent antiepileptic properties with a relatively mild adverse effect profile makes LEV an attractive adjunctive therapy for partial seizures.
Animals↗
A crossover, add-on trial of talampanel in patients with refractory partial seizures.
The authors report a double-blind, placebo-controlled, crossover study of talampanel in 49 patients with refractory partial seizures. Three doses of talampanel were investigated based on differences in patients' concomitant antiepileptic drug usage. Talampanel showed efficacy in reducing seizure frequency (p = 0.001) with a median seizure reduction of 21%. Eighty percent of patients had fewer seizures on talampanel than on placebo. Dizziness (52%) and ataxia (26%) were the only significant adverse events.
Adult↗
Anterior commissure absence without callosal agenesis: a new brain malformation.
The authors report a novel human brain malformation characterized by the absence of the anterior commissure without callosal agenesis, but associated with gross unilateral panhemispheric malformation incorporating subependymal heterotopia, subcortical heterotopia, and gyral abnormalities including temporal malformation and polymicrogyria. In contrast, a normal anterior commissure was found in 125 control subjects and in 113 other subjects with a range of brain malformations.
Adolescent↗
The problem of the drug-resistant epilepsies.
For the majority of patients with epilepsy, the prognosis for seizure control is very good; however, refractory epilepsy develops in about 20-30% of patients and represents a significant challenge for both clinical management and for research. Physicians treating epilepsy are often asked to predict prognosis and make decisions about commencing and withdrawing treatment. Practice can be guided by epidemiological studies of prognosis. It seems that prognosis depends largely on the aetiology of the seizures and the clinical background of the patient rather than on the seizures themselves or the treatment prescribed. Aetiologies are, however, not the sole determinant of outcome and response to treatment and unknown factors must exit. It is likely that some of these unknown factors are genetically determined but this needs confirmation. The search for these unknown factors that may determine intractability in epilepsy is a very exciting prospect, which may prove to be multifactorial. In some patients, epilepsy may indeed become resistant to treatment whilst in others the propensity for intractability to the drugs currently available may be part and parcel of the condition. Further research is urgently needed to elucidate the full range of mechanisms that lead to drug resistant epilepsy.
Adolescent↗
Information recalled by women taking anti-epileptic drugs for epilepsy: a questionnaire study.
Women with epilepsy have different needs from men, particularly associated with childbearing. Despite clinical guidelines, the care of women with epilepsy remains suboptimal. The aim of this study was to establish whether women with epilepsy recall being given information on topics relating to childbearing. Design of study and methods included a postal questionnaire study of 795 women with epilepsy and of childbearing age. The respondents were identified through both general practices and hospital clinics as part of the Clinical Standards Advisory Group study into Epilepsy Services. Of those women who considered the questions personally relevant, 38-48% recalled receiving information about contraception, pre-pregnancy planning, folic acid and teratogenicity, with lower overall proportions among adolescent women. The proportions that recalled receiving information about vitamin K, safety in child-care and breast-feeding were lower at 12, 24 and 24%, respectively. While it is recognised that information provided may not be recalled, our results suggest that further measures are required to improve the effectiveness of information provision in the UK in relation to women of childbearing age with epilepsy.
Adolescent↗
The epidemiology of epilepsy: the size of the problem.
The prevalence of epilepsy is generally taken as between 5 and 10 cases per 1000 persons, and the overall incidence as about 50 cases per 100,000 persons. The rates are dependent on case ascertainment and on definitions used. The prognosis depends on many factors, including the number of seizures at presentation, the seizure type and the use of anti-epileptic drugs. Epilepsy carries an excess mortality; the cause of death can be unrelated to epilepsy, related to the underlying disease causing epilepsy, or related to epilepsy itself.
Epilepsy↗
Long-term continuation of levetiracetam in patients with refractory epilepsy.
The long-term continuation (retention) rate, efficacy, and safety data of the new antiepileptic drug levetiracetam (LEV) was evaluated in all patients with epilepsy exposed to the drug during its developmental program (n = 1,422). The retention rate was estimated to be 60% after 1 year and 32% after 5 years. Thirty-nine percent (512/1,325) of patients had a seizure reduction of > or =50%, and 13% (183/1,422) became seizure-free for at least 6 months. LEV seems an effective and well tolerated new antiepileptic drug.
Adolescent↗
A longitudinal quantitative MRI study of community-based patients with chronic epilepsy and newly diagnosed seizures: methodology and preliminary findings.
Experimental and human data suggest that progressive cerebral damage may result from the cumulative effect of brief recurrent seizures. Longitudinal studies addressing this fundamental question, however, are lacking. We have addressed this need with a large prospective community-based observational study, which aims to rescan 154 patients with chronic active epilepsy and 90 patients with newly diagnosed seizures, after an interval of 3.5 years. Here, we describe the quantitative magnetic resonance methods used to identify subtle volume changes in hippocampal, cerebellar, and neocortical structures over time and report preliminary findings. Using this methodology, we have previously shown that we can reliably detect individual hippocampal volume (HV) and cerebellar volume (CBV) changes greater than 3.1 and 3.0%, respectively (Lemieux et al, 2000). Analysis of the first 53 subjects (24 patients with chronic active epilepsy, 9 patients with newly diagnosed seizures, and 20 controls) has demonstrated significant HV losses in 4 individuals. Automated and semiautomated calculation has detected significant reductions in CBV, total brain volume, and gray matter volume in 2, 3, and 1 subject, respectively. There were no significant white matter volume losses detected. Data collected from rescanning the entire cohorts will help to provide further information on the relationship between recurrent seizures and secondary brain damage.
Adult↗
Comparing the cost of epilepsy across eight European countries.
To observe the degree to which prices for medical services and anti-epileptic drugs (AEDs) vary between eight European Union (EU) countries, to identify the factors that are likely to contribute to these variations and to consider the validity of international cost-of-illness comparisons. Cost-of-illness study methodology has been used to estimate the national cost of epilepsy in several developed countries. The validity of comparing these studies is unknown. Eight EU member countries were selected. Charges and prices were obtained for important aspects of medical care of patients with epilepsy including AEDs. The perspective taken was that of the major health care payer within each country. Prices were validated by a local panel of doctors expert in treating epilepsy. Prices for similar services were compared between countries. Charges and prices levied to health service payer vary widely between the eight countries considered. The cheapest and most expensive medical services vary by as much as 24 times, whereas the price of AED varies up to 4.4 times. These wide variations suggest that prices do not reflect the true cost of providing these important aspects of epilepsy treatment. International comparisons between national cost-of-illness estimates relying on such prices should be interpreted with caution.
Anticonvulsants↗
The epidemiology of epilepsy and learning disability.
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Adolescent↗
A pharmacoepidemiologic study of factors influencing the outcome of treatment with lamotrigine in chronic epilepsy.
PURPOSE: To identify prognostic factors for freedom from seizures and long-term retention of treatment in patients receiving lamotrigine (LTG). METHODS: A multicenter, retrospective, case record study of 1,050 patients with chronic epilepsy was carried out. Logistic regression and Cox regression analyses were used to identify clinical features associated with freedom from seizures and retention of treatment, respectively. Long-term retention rates of LTG therapy were estimated using Kaplan-Meier survival analysis. RESULTS: The 1,050 patients with chronic epilepsy were included in the study. Patients with generalized epilepsy (p = 0.01), who were not receiving carbamazepine (CBZ; p = 0.02) were more likely to become seizure-free. Sixty percent of patients continued on LTG therapy >1 year and estimated retention at 8 years was 38%. Patients with generalized epilepsy (p = 0.002), patients receiving concurrent sodium valproate (VPA; p < 0.0001), those not previously exposed to gabapentin and vigabatrin (p < 0.0001), and those in whom the starting dose was lower (p < 0.0012), were more likely to remain on long-term treatment with LTG. The relationships with exposure to other antiepileptic drugs remained significant in patients with focal and with generalized epilepsy when considered separately. CONCLUSIONS: The best results from LTG treatment in terms of freedom from seizures and long-term retention of treatment were obtained in patients with generalized epilepsy. Retention of treatment was enhanced by VPA not only in generalized but also in focal epilepsy. The importance of a low starting dose of LTG was again confirmed. The apparent negative effect of CBZ in patients taking LTG merits further investigation.
Anticonvulsants↗
Adverse event monitoring in lamotrigine patients: a pharmacoepidemiologic study in the United Kingdom.
PURPOSE: This postmarketing surveillance study of lamotrigine (LTG) was performed to provide complementary data to large-scale Prescription-Event Monitoring study with a retrospective case records survey in five tertiary referral epilepsy centres in the United Kingdom. METHODS: Adverse events were recorded and compared with those of two other new antiepileptic drugs (AEDs), gabapentin (GBP) and vigabatrin (VGB). All deaths were followed up and standardised mortality ratios (SMRs) were calculated. Serious adverse events were assessed individually. RESULTS: A total of 2,701 patients was identified as being exposed to LTG and/or the comparators. It was necessary to exclude 1,326 patients because LTG and/or comparators had been commenced outside the study centres. The adverse events with LTG reported by this study were similar to those reported in the literature. Skin rash was the major adverse event. Life-threatening hepatic failure, acute exacerbation of ulcerative colitis, disseminated intravascular coagulation, and renal failure were reported. No death could be directly attributed to the use of LTG. The SMR was slightly higher than that reported in the literature; this probably reflects severity of epilepsy in the study population. CONCLUSIONS: The safety profile of LTG was similar to that in the large-scale Prescription-Event Monitoring study and generally acceptable. Life-threatening adverse reactions were rare.
Acetates↗
The treatment gap in epilepsy: the current situation and ways forward.
This article is a summary of a workshop held by the ILAE concerning the issue of the epilepsy treatment gap in developing countries. The gap is defined in terms of those people with epilepsy who are not being appropriately treated and is the result of an array of medical, political, social, economic, and cultural factors. The situation regarding the treatment gap for various countries is reviewed, along with some of its causes. Although the overall gap is estimated to be large, a number of recent projects and interventions have been effective in delivering appropriate treatment to people with epilepsy in underresourced countries of the developing world. It is hoped that these may be transferable elsewhere and that, combined with the ILAE/IBE/WHO Global Campaign against Epilepsy and increased support from the worldwide epilepsy community, the treatment gap will begin to be bridged.
Anticonvulsants↗
The epidemiology of epilepsy: the size of the problem.
The prevalence of epilepsy is generally taken as between 5 and 10 cases per 1000 persons, and the overall incidence as about 50 cases per 100 000 persons. The rates are dependent on case ascertainment and on definitions used. The prognosis depends on many factors, including the number of seizures at presentation, the seizure type and the use of anti-epileptic drugs. Epilepsy carries an excess mortality; the cause of death can be unrelated to epilepsy, related to the underlying disease causing epilepsy, or related to epilepsy itself.
Epilepsy↗
The clinical impact of epilepsy genetics.
An overemphasis on molecular genetic advances in epilepsy is in danger of missing the major contribution that clinical genetic studies make in predicting the likely benefit of molecular research efforts. Genetic epidemiology, twin, and family studies suggest that some individual epilepsy genes raise the risk for developing many different types of epilepsy but that specific combinations of these genes determine specific epilepsy phenotypes. Experimental data show how differences in drug response can result from inherited differences in drug sensitivity and there is emerging data on the genetic basis of harmful adverse drug reactions and teratogenesis. These developments predict a future in which epilepsy is ultimately classified on the basis of its oligogenic architecture, effective treatments are tailored to the appropriate patient and harmful adverse drug reactions avoided in those who are sensitive.
Epilepsy↗
The dynamics of drug treatment in epilepsy: an observational study in an unselected population based cohort with newly diagnosed epilepsy followed up prospectively over 11-14 years.
OBJECTIVES: To study prospectively long term dynamics and patterns of treatment in a population based cohort of patients with newly diagnosed epilepsy. METHODS: 564 patients with definite epilepsy entered the UK National General Practice Study of Epilepsy (NGPSE), between 1984 and 1987, and were prospectively followed up for between 11-14 years. RESULTS: Treatment was started in 433 (77%) patients. Only 15% of single seizure patients had medication prescribed initially, although due to high seizure recurrence, more than 70% ultimately received antiepileptic medication. 209/564 patients (37%) were on drug therapy for epilepsy at the time of last follow up. 168/564 patients (30%) have stayed continuously on medication and another 41/564 patients (7%) restarted drug therapy because of seizure recurrence, having withdrawn medication. 98/209 (47%) of those on treatment are known to be in 5 year terminal remission. Phenytoin (29%) and carbamazepine (27%) were the most commonly preferred first line drugs followed by valproate (15%). Less than half of treated patients with partial seizures received carbamazepine as a first line drug and less than a third with generalised seizures were prescribed valproate as first choice drug. Nine out of 31 (29%) patients with one or more seizures a week at last follow up had never tried a second drug and only seven (23%) had tried four or more drugs. 11% of all treatment changes involved a new antiepileptic drug. Treatment changes were associated with low terminal remission rates. CONCLUSIONS: Out of 30 000 patients with newly diagnosed epilepsy every year in the United Kingdom, about 6000 have inadequate seizure control in the long term. About a third of the patients in this group have one or more seizures every month. Only two thirds of these patients with frequent seizures are likely to switch medication to try and achieve better seizure control. There is probably still considerable room for improvement in prescribing practice in the United Kingdom.
Adolescent↗
Temporal lobe epilepsy following febrile seizures: unusually prolonged latent periods.
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Adult↗