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Een 24-jarige onderwijzeres is met haar klas op schoolkamp. Op de derde ochtend van het kamp maakt een leerlinge haar wakker na enkele uren slaap. Direct na het wekken slaakt de onderwijzeres een kreet, gevolgd door een gegeneraliseerde stijfkramp, trekkingen en een tongbeet. De aanval duurt enkele minuten, waarna ze in een postictaal coma blijft liggen. Een ambulance wordt gewaarschuwd. Wanneer deze arriveert is de aanval voorbij, maar ze is verward en slecht georienteerd. Ze wordt op de spoedeisende hulp (seh) van het plaatselijke ziekenhuis gezien, waar geen neurologische en algemeen lichamelijke afwijkingen worden gezien.

Objectives Mesial temporal lobe epilepsy syndrome (MTLE) with specific electrophysiological and clinical characteristics and hippocampal sclerosis (HS) on MRI is considered the prototype of a syndrome with good surgical prognosis. Ictal onset zones in MTLE have been found to extend outside the hippocampus and neocortical seizures often involve mesial structures. It can, thus, be questioned whether MTLE with HS is different from lesional temporal epilepsies with respect to electro-clinical characteristics and surgical prognosis. We assessed whether MTLE with HS is distinguishable from lesional TLE and which criteria determine surgical outcome. Methods People in a retrospective cohort of 389 individuals with MRI abnormalities who underwent temporal lobectomy, were divided into “HS only” or “lesional” TLEs. Twenty-six presented with dual pathology and were excluded from further analysis. We compared surgical outcome and electro-clinical characteristics. Results Over half (61%) had “HS only.” Four electro-clinical characteristics (age at epilepsy onset, febrile seizures, memory dysfunction and contralateral dystonic posturing) distinguished “HS only” from “lesional” TLE, but there was considerable overlap. Seizure freedom 2 years after surgery (Engel class 1) was similar: 67% (“HS only”) vs 69% (“lesional” TLE). Neither presence of HS nor electro-clinical criteria was associated with surgical outcome. Conclusions Despite small differences in electrophysiological and clinical characteristics between MTLE with HS and lesional TLE, surgical outcomes are similar, indicating that aetiology seems irrelevant in the referral for temporal surgery.

Item does not contain fulltext In recent years, several new antiepileptic drugs (AEDs) have been licensed: felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, vigabatrin and zonisamide. These drugs have proven efficacy as add-on therapy in patients with difficult-to-treat partial epilepsy, as 20-50% of patients treated in add-on trials experienced a seizure reduction of >or=50%. Relatively few trials have been conducted to evaluate these drugs as monotherapy for patients with newly diagnosed epilepsy. In the monotherapy trials that have been conducted, the newer drugs were often as efficacious as conventional drugs, and their tolerability was often better. However, the methodology of these trials can be criticised. Because of the relative lack of robust data for the newer agents, the conventional drugs have thus far maintained their status as first-line monotherapy. However, when first-line monotherapy fails, an alternative drug has to be chosen from the available conventional and newer drugs.This article aims to give detailed background information on the newer AEDs in order to enable physicians to make a rational choice from the available drugs for individual patients. Data are provided for the different newer AEDs on mechanisms of action; efficacy in refractory partial epilepsy, newly diagnosed epilepsy in adults and generalised seizure types; adverse effects; pharmacokinetics; and use in special patient categories.

AIMS: To investigate the pharmacokinetic and pharmacodynamic profile of midazolam administered as a concentrated intranasal spray, compared with intravenous midazolam, in healthy adult subjects. METHODS: Subjects were administered single doses of 5 mg midazolam intranasally and intravenously in a cross-over design with washout period of 1 week. The total plasma concentrations of midazolam and the metabolite 1-hydroxymidazolam after both intranasal and intravenous administration were described with a single pharmacokinetic model. beta-band EEG activity was recorded and related to midazolam plasma concentrations using an exponential pharmacokinetic/pharmacodynamic model. RESULTS: Administration of the intranasal spray led to some degree of temporary irritation in all six subjects, who nevertheless found intranasal administration acceptable and not painful. The mean (+/-s.d.) peak plasma concentration of midazolam of 71 (+/-25 ng ml-1) was reached after 14 (+/-5 min). Mean bioavailability following intranasal administration was 0.83+/-0.19. After intravenous and intranasal administration, the pharmacokinetic estimates of midazolam were: mean volume of distribution at steady state 1.11+/-0.25 l kg-1, mean systemic clearance 16.1+/-4.1 ml min-1 kg-1 and harmonic mean initial and terminal half lives 8.4+/-2.4 and 79+/-30 min, respectively. Formation of the 1-hydroxymetabolite after intranasal administration did not exceed that after intravenous administration. CONCLUSIONS: In this study in healthy volunteers a concentrated midazolam nasal spray was easily administered and well tolerated. No serious complications of the mode of administration or the drug itself were reported. Rapid uptake and high bioavailability were demonstrated. The potential of midazolam given via a nasal spray in the acute treatment of status epilepticus and other seizure disruptions should be evaluated.

The use of carbamazepine (CBZ) and oxcarbazepine (OXC) as first-line antiepileptic drugs in the treatment of focal epilepsy is limited by hyponatremia, a known adverse effect. Hyponatremia occurs in up to half of people taking CBZ or OXC and, although often assumed to be asymptomatic, it can lead to symptoms ranging from unsteadiness and mild confusion to seizures and coma. Hyponatremia is probably due to the antidiuretic properties of CBZ and OXC that are, at least partly, explained by stimulation of the vasopressin 2 receptor/aquaporin 2 pathway. No known genetic risk variants for CBZ- and OXC-induced hyponatremia exist, but likely candidate genes are part of the vasopressin water reabsorption pathway.

The antiepileptic drug primidone is to be withdrawn from sale by January 2004. After this date, the drug will still be available for a time, but only on a limited basis. Most primidone users are elderly patients who have been prescribed this drug for many years. Changing to a new drug constitutes a health risk for them. If primidone treatment is discontinued too quickly, withdrawal seizures may appear, some of which may be severe. In patients who have not suffered an epileptic seizure for many years, discontinuing medication may be considered. Whenever continuation of anticonvulsive treatment is desirable, it may probably be a good idea to switch over to some newer antiepileptic drug. If a simple and quick substitution is essential, primidone may be replaced by its main metabolite: phenobarbital. General practitioners and neurologists are strongly advised to alter patients' medication in good time.

Progressive myoclonus epilepsy type 1 of Unverricht-Lundborg (EPM1) is a rare disorder, associated with mutations in the cystatin B (CSTB) gene. The most prevalent molecular abnormality is an expansion of a dodecamer repeat in the promoter region of the CSTB gene, but point mutations in the CSTB gene have also been found. DNA examination may be useful in discriminating EPM1 from juvenile myoclonic epilepsy, and from other types of progressive myoclonus epilepsy. An early diagnosis is important to optimise treatment and to provide an adequate prognosis and prediction of recurrence.

In an editorial , Marson and Chadwick review some of the evidence for the effectivity and tolerability of new drug treatments for epilepsy.1 They discuss the role of randomised clinical trials for providing data that satisfy the requirements of the licensing bodies but that do not reflect day to day clinical practice. With oxcarbazepine (Trileptal®) we recently experienced another complicating factor, a change in formulation, which may influence interpretation of results of clinical trials. Oxcarbazepine had recently been licensed in the United Kingdom and the United States but was already registered in The Netherlands in 1991. In our epilepsy centre we have had extensive clinical experience with oxcarbazepine since 1986.2 In 2001 we noticed new symptoms such as diplopia, dizziness, …

The authors describe 12 pregnancies in women with epilepsy using lamotrigine (LTG) monotherapy. A seizure increase in nine pregnancies was probably related to a gradual decline of LTG level-to-dose ratio to 40% of baseline. After delivery, LTG kinetics returned swiftly to baseline, causing toxic side effects in some women. Frequent LTG level monitoring and appropriate dose adjustments are advised in the period before and during pregnancy and after delivery, especially in women on LTG monotherapy.