C. A. van Donselaar

Levetiracetam: preliminary experience in patients with primary brain tumours.

Epilepsy in patients with brain tumours is common. The incidence of seizures varies from 20 to 70% with the highest incidence in low-grade gliomas (60–70%) 1. There is an increasing use of systemic chemotherapy in patients with brain tumours, and this raises the concern on the potential of substantial interactions between AEDs and anti-neoplastic agents. Phenytoin, carbamazepine, phenobarbital, and to a lesser extent valproate, oxcarbazepine and topiramate, are metabolised by the hepatic cytochrome P-450 system, especially the CYP 2C9, CYP 2C19, CYP 3A4 and CYP 2B1 iso-enzyme 2, 3. To a more or lesser extent, all these AEDs have inductory or inhibitory effects on one or more iso-enzymes. Many chemotherapeutic agents also are metabolised by the hepatic CYP system4. Glucocorticoids are of special interest in patients with brain tumours. Dexamethasone is metabolised by CYP 3A4, and mostly induces it 5. Levetiracetam (LEV), a novel AED, has no known pharmacological interactions as it has no effect on mixed function oxidase liver enzymes and has no protein-binding properties 6. Therefore, LEV may be a particularly useful drug in this group of patients. We performed a prospective feasibility study to evaluate the safety and efficacy of LEV in this patient group.

Complaints associated with the use of antiepileptic drugs: results from a community-based study

BACKGROUND Few data exist with respect to the occurrence of chronic side effects due to antiepileptic drugs (AED) in routine clinical practice. OBJECTIVE To evaluate the prevalence of subjective complaints which patients with epilepsy regard as side effects of their AED treatment in a community-based population. METHODS Cross-sectional study. Subjects were identified through the database of AED-use in the pharmacies in a suburban area in The Netherlands. Respondents completed a brief questionnaire about their epilepsy, including a checklist with 30 complaints, which are common in AED users. RESULTS We present data of 346 responding adults with treated epilepsy from a population of 107,000 adult inhabitants. Eighty percent was using monotherapy, with few patients taking new AEDs. Almost 60% of the patients reported complaints probably due to side effects in at least three domains. General CNS-related side effects were reported most often; memory problems (21.4% of the patients) and fatigue (20.3%) were dominant. Polytherapy was associated with more side effects than monotherapy. We identified differences in profiles of complaints between valproate, carbamazepine and phenytoin monotherapy. Complaints were not substantially associated with ongoing seizures or other treatment factors. CONCLUSIONS The majority of patients taking AEDs for epilepsy think they have side effects form their drugs, even when seizures were in remission and when monotherapy was used. Our findings suggest a need to improve monitoring of complaints of side effects of AEDs and to explore the feasibility of interventions aimed at reduction of such complaints in everyday clinical practice.

A cross-sectional study of subjective complaints in patients with epilepsy who seem to be well-controlled with anti-epileptic drugs

OBJECTIVES Side-effects of anti-epileptic drugs (AEDs) may be overlooked in patients with epilepsy in everyday clinical practice. The aim of this study was to assess the prevalence and severity of subjective complaints in patients who were considered to be well-controlled and to assess whether these complaints are related to medication, personality traits, or other determinants. METHODS We included patients with epilepsy who were considered to be well-controlled in a cross-sectional study in seven hospitals in the Netherlands. Their medication had not been changed for six months and an apparent reason to change the medication was lacking at the time of enrolment. Subjective complaints were assessed with a 46-item questionnaire. Using multivariable linear regression modeling, we assessed whether patient characteristics, epilepsy characteristics, medication, quality of life (Qolie-10), and personality traits (SCL-90) explained the presence and severity of complaints. RESULTS Of 173 included patients, 67% reported moderate to severe subjective complaints on the questionnaire. Cognitive complaints were reported most frequently. Multivariate modeling showed that 61% of the variance in reported complaints could be explained by included determinants. The prevalence and severity of complaints was associated with AED polytherapy and higher scores on psycho neuroticism. CONCLUSIONS Patients who were considered to be well-controlled proved to report an unexpectedly high number of subjective complaints. Both medication and aspects of personality contributed to the level of complaints. Our study illustrates that subjective side-effects are easily overlooked in everyday clinical practice, possibly because in practice a generally phrased question is used to detect side-effects.

The Diagnostic Yield of a Second EEG After Partial Sleep Deprivation: A Prospective Study in Children with Newly Diagnosed Seizures

Summary: Purpose: To assess the diagnostic yield of a repeated EEG (REPEEG) after partial sleep deprivation (SD) in children and adolescents with one or more seizures who previously had had a standard EEG (STDEEG) without epileptiform abnormalities (EAs). In the literature, 32–75% of such REPEEGs after SD were reported to show EA.

Adjustment of treatment increases quality of life in patients with epilepsy: a randomized controlled pragmatic trial

Background and purpose:  Complaints about side‐effects of antiepileptic drugs (AEDs) may be overlooked in clinical practice. We assessed the value and risks of an active intervention policy for reported complaints in a randomized controlled pragmatic trial.

Immunoglobulins in children with epilepsy: the Dutch Study of Epilepsy in Childhood

In an unselected cohort of 282 children, serum immunoglobulin (Ig) concentrations were determined shortly after the first presentation with one or more unprovoked epileptic seizures and before the start of treatment with anti‐epileptic drugs (AEDs), and after 9–18 months of AEDs use. At intake, IgA, IgG1, IgG2 and IgG4 concentrations were significantly higher than published reference values in healthy age‐matched controls. In a subset of 127 children, Ig levels at intake were compared with those after AEDs use for 9–18 months. IgA and IgG4 levels had decreased significantly to normal concentrations, but IgG1 and IgG3 levels increased significantly. To determine the influence of AEDs, Ig levels in children who used carbamazepine or valproic acid monotherapy were analysed separately. The use of carbamazepine was associated with a significant decrease of IgA and IgG4 levels, and the use of valproic acid with a significant decrease of IgA and increase of IgG1 levels. In conclusion, humoral immunity is already altered in children shortly after the first presentation with epileptic seizures. Whether this is the consequence of an exogenous event, and to what extent this is related to an interaction of the central nervous system and the immune system, remains to be evaluated. Treatment with AEDs, such as carbamazepine and valproic acid, is associated with significant changes of Ig (sub)class concentrations.

Cost Minimization Analysis of Antiepileptic Drugs in Newly Diagnosed Epilepsy in 12 European Countries

Summary A recent United Kingdom cost minimization analysis (CMA) of four antiepileptic drugs (AEDs) used to treat newly diagnosed adult epilepsy demonstrated that a new drug, lamotrigine (LTG), incurred higher costs than carbamazepine (CBZ), phenytoin (PHT), and valproate (VPA), whose costs were similar. This analysis took account of each drugs side‐effect and tolerability profile. The present analysis investigated the costs of treatment with LTG, CBZ, PHT, and VPA in 12 European countries. Data were derived from published sources and from a panel of locally based experts. When no published data were available, estimates were obtained using expert opinion by a consensus method. These data were incorporated into a treatment pathway model, which considered the treatment of patients during the first 12 months after diagnosis. The primary outcome considered was seizure freedom. Randomized controlled trials demonstrate that the drugs considered are equally effective in terms of their ability to achieve seizure freedom, and thus the most appropriate form of economic evaluation is a CMA. These trials provided data on the incidence of side effects, dosages, and retention rates. The economic perspective taken was that of society as a whole and the analysis was calculated on an “intent‐to‐treat” basis. Only direct medical costs were considered. In each country considered, LTG was twofold to threefold more expensive than the other drugs considered. A sensitivity analysis demonstrated that varying each of the assumptions (range defined by expert panels) did not significantly alter the results obtained.

Nonsymptomatic generalized epilepsy in children younger than six years: Excellent prognosis, but classification should be reconsidered after follow-up: The Dutch study of epilepsy in childhood

Summary:  Purpose: To assess the prognosis and the accuracy of the epilepsy classification in young children with nonsymptomatic generalized epilepsy.

Long-term outcome of benign childhood epilepsy with centrotemporal spikes: Dutch Study of Epilepsy in Childhood

001 INFANTILE ONSET FOCAL EPILEPSY AND EPILEPTIC ENCEPHALOPATHIES ASSOCIATED WITH PCDH19 GENE MUTATIONS: NEW DE NOVO AND FAMILIAL MUTATIONS Marini C, Mei D, Parmeggiani L, Norci V, Calado E, Moreira A, Ferrari A, Pisano T, Battaglia D, Guerrini R Neurology Unit, Pediatric Hospital A. Meyer, Florence, Italy, Azienda Sanitaria di Bolzano, Servizio Interaziendale di Neuropsichiatria Infantile e dell’Adolescenza, Bolzano, Italy, Pediatric Neurology Unit, Hospital Dona Estefania, Lisbon, Portugal, Neurology and Psychiatric Unit, IRCCS Fondazione Stella Maris, Calambrone, Pisa, Italy, Child Neurology Unit, Policlinico Universitario Gemelli, Roma, Italy, University of Florence, Florence, Italy