We evaluated the efficacy of vagus nerve stimulation (VNS) in Genetic Absence Epilepsy Rats from Strasbourg (GAERS), a validated model for absence epilepsy. In the first experiment, we investigated whether VNS applied at seizure onset can interrupt spike and wave discharges (SWD). In the second experiment, we investigated whether SWD are suppressed or shortened in duration when VNS is applied several hours per day. Both control and VNS groups underwent EEG and VNS electrode implantation. For the first experiment, a randomized crossover design was used. Stimuli (amplitude: 3 V; frequency: 30 Hz; pulse duration: 500 μs) were given when an SWD occurred on the EEG. The experiment was repeated the next day. In the second experiment, treated animals were stimulated (amplitude: 1.5 mA; frequency: 30 Hz; pulse duration: 500 μs; on/off time cycle: 30 s/5 min) for 3 h per day, during five consecutive days. In the first experiment, the duration of the SWD was increased on day 1, (P < 0.05). There was no difference in SWD duration on Day 2. In the second experiment, no significant differences could be found in number, duration and EEG frequency of SWD. VNS applied at the onset of an SWD can prolong the duration of SWD in GAERS. As a 5-day stimulation protocol had no effect, long-term VNS might be necessary to affect SWD.

Summary: Purpose: More than 20% of epilepsy patients have refractory seizures. Treatment options for these patients include continued polytherapy with/without novel antiepileptic drugs (AEDs), epilepsy surgery (ES), or vagus nerve stimulation (VNS). The purpose of this study was prospectively to compare epilepsy‐related direct medical costs (ERDMCs) incurred by these different treatment modalities. Methods: Eighty‐four patients underwent a complete presurgical evaluation protocol at our institution. As a result, 24 (29%) patients were treated with continued AED polytherapy only; 35 (40%) underwent ES; and 25 (30%) had VNS. In each patient, annual costs in the 2 years preceding the therapeutic decision (ERDMC‐pre) and during the follow‐up afterward (ERDMC‐post) were prospectively calculated. Furthermore, frequency of complex partial seizures with/without secondary generalization (CPS±SG), dosage and number of AEDs, number of hospital admission days, clinic visits, and laboratory tests before and after the therapeutic decision also were prospectively assessed. ERDMC‐pre and ERDMC‐post were compared in and among the three treatment groups. Results: In patients conservatively treated with AEDs, mean frequency of CPSs decreased from 12 per month to nine per month, whereas mean ERDMCs decreased from $2,525 U.S. to $2,421 U.S. In surgical patients, mean seizure frequency decreased from six to fewer than one per month; mean ERDMCs per year decreased from $1,465 U.S. preoperatively to $1,186 U.S. postoperatively. In the VNS group, mean seizure frequency decreased from 21 per month to seven per month. ERDMCs in this subgroup decreased from $4,826 U.S. to $2,496 U.S. Mean seizure frequency changes were significant when conservatively treated patients were compared with surgically treated and VNS patient groups (χ 2 test, p<0.001 and p = 0.0019, respectively). ERDMC changes in conservatively treated patients also were statistically significant when compared with surgically treated and VNS patients (χ 2 test, p = 0.0007 and p = 0.0036, respectively). No statistically significant differences were found in ERDMC changes between the surgical and VNS groups (χ 2 test, p = 0.387). Conclusions: Ongoing daily treatment of patients who underwent resective surgery costs significantly less than conservative treatment. For patients in whom resective surgery is not an option, ERDMC show a significant decrease in VNS‐treated patients compared with conservatively treated patients.

Rationale.Vagus nerve stimulation (VNS) by intermittent and programmed electrical stimulation of the left vagus nerve in the neck, has become widely available. It is an effective treatment for patients with refractory epilepsy. Patients can be provided with a magnet that allows to deliver additional stimulation trains. Since earlier studies have demonstrated the persistence of a stimulation effect after discontinuation of the stimulation train, we evaluated the clinical efficacy of VNS both in the programmed intermittent stimulation mode and magnet stimulation mode.

Vagus nerve stimulation (VNS) is an effective alternative treatment for patients with refractory epilepsy. The generator produces intermittent stimulation trains and does not require patient intervention. Using currently available technology, continuous stimulation is incompatible with a reasonable battery life. Because earlier studies have demonstrated the persistence of a stimulation effect after discontinuation of the stimulation train, we intended to evaluate the clinical efficacy of VNS in both the programmed intermittent stimulation mode and the magnet stimulation mode. Patients, companions, and caregivers were instructed on how to administer additional stimulation trains when an aura or a seizure onset occurred. We assumed that patients or caregivers could recognize habitual seizures and were able to evaluate sudden interruption of these seizures. During a mean follow-up of 35 months, 46% of patients became responders, with a reduction in seizure frequency of more than 50%. Twenty-nine percent of patients stopped having convulsive seizures. In two thirds of patients who were able to self-administer or receive additional magnet stimulation, seizures could be interrupted consistently or occasionally. More than half of the patients who reported a positive effect of magnet stimulation became responders. Only three patients were able to use the magnet themselves. In most cases, support from caregivers was necessary. This study is the first to document the efficacy of magnet-induced VNS in a larger patient population during long-term follow-up. The magnet is a useful tool that provides patients who are treated with VNS and mainly caregivers of such patients with an additional means of controlling seizures. To further confirm the self-reported results from our patients, additional studies comparing programmed stimulation and magnet-induced stimulation during monitoring conditions are needed.

The performance of the three-shell spherical head model versus the performance of the realistic head model is investigated when solving the inverse problem with a single dipole, in the presence of noise. This is evaluated by inspecting the average dipole location error when applying a spherical and a realistic head model, for 1000 noisy scalp potentials, originating from the same test dipole and having the same noise level. The location errors are obtained utilizing a local linearization, which is validated with a Monte Carlo simulation. For 27 electrodes, an EEG epoch of one time sample and spatially white Gaussian noise we found that the importance of the realistic head model over the spherical head model reduces by increasing the noise level.

Every two years the European Chapters of the International Bureau for Epilepsy meet for a conference which includes people with epilepsy themselves and representatives of the various national organizations that speak for and promote the cause and interests of people with epilepsy in their various countries. There is both an information exchange and a meeting of minds and a developing 'European' awareness. Part of the conference is based on patient education, lectures mainly given for a lay audience by a medical faculty: part is based on what one might term the necessary business of epilepsy organizations and of the IBE itself: and part is a tacked-on medical educational conference for doctors (mainly from the host country). This latter element is there, I suspect, in order to help fund the rest of the conference as it invites sponsorship that might otherwise not be obtainable. I was asked, as Editor of the European Journal of Epilepsy, whether I would publish the abstracts of the meeting. I am able to publish a selection: there were far too many to publish as a whole, without sponsorship. My choice is probably idiosyncratic but is guided by my impressions of the conference itself and by certain other reasons. Firstly, language: if European unity of purpose is to be achieved for epilepsy we need a common language. This has to be English. A few hundred years ago the universal common language of educated Europe was Latin: later it was French: if the other side had won in 1939–45, it would have been German: but now it is English. Most educated Europeans accept that. The French disagree. But if they want their language to be the universal European language they are going the wrong way about it: grimly holding on to the purity of your language, its words and grammar, so that it becomes an esoteric obstacle course for the uninitiated is not the way to make it a universal language, but merely an excuse for other people to shun it. English, by contrast, borrows words from every other language, has mixed Germanic, French and romantic roots and, if it has a grammar, its nuances are unknown to its native speakers. This lack of formal grammar means that it is possible to speak it very badly and yet be understood. English is changing: there are several distinct versions—southern English, northern English (at least two of those), Scots English, …

Purpose: Left-sided vagus nerve stimulation (VNS) is an efficacious treatment for patients with refractory epilepsy. The precise mechanism of action remains to be elucidated. Only limited data on VNS-induced changes in regional cerebral blood flow (rCBF) are available. The aim of this study was to investigate rCBF changes during initial VNS with single-photon emission computed tomography (SPECT).Methods: In 12 patients (8 women, 4 men) with mean age of 32 years and mean duration of epilepsy of 19 years, VNS-induced rCBF changes were studied by means of a Tc-99m-ethyl cysteinate dimer activation study with a single-day split-dose protocol before and immediately after initial stimulation. Images were acquired on a triple-head camera with fan-beam collimators and were reconstructed with scatter and attenuation correction. After coregistration to a standardized template, both a semiquantitative analysis using predefined volumes-of-interest (VOIs) as well as voxel-by-voxel analysis of the intra-subject activation were performed. During follow-up, efficacy of VNS in terms of seizure-frequency reduction was studied.Results: The semiquantitative analysis, with reference to the total counts in all VOIs, revealed a significant decrease of activity in the left thalamus immediately after the initial stimulation train. These results agreed with voxel-by-voxel analysis. In our study ipsilateral thalamic hypoperfusion was the most significant finding. Mean frequency of complex partial seizures was reduced from 30 per month before implantation to six per month after implantation.Conclusions: VNS induces rCBF changes immediately after initial stimulation that can be studied with SPECT. VNS-induced changes in the thalamus may play an important role in suppression of seizures. However, no significant relation between the level of hypoperfusion and subsequent clinical efficacy was found.

Localization of focal electrical activity in the brain using dipole source analysis of the electroencephalogram (EEG), is usually performed by iteratively determining the location and orientation of the dipole source, until optimal correspondence is reached between the dipole source and the measured potential distribution on the head. In this paper, we investigate the use of feed-forward layered artificial neural networks (ANNs) to replace the iterative localization procedure, in order to decrease the calculation time. The localization accuracy of the ANN approach is studied within spherical and realistic head models. Additionally, we investigate the robustness of both the iterative and the ANN approach by observing the influence on the localization error of both noise in the scalp potentials and scalp electrode mislocalizations. Finally, after choosing the ANN structure and size that provides a good trade off between low localization errors and short computation times, we compare the calculation times involved with both the iterative and ANN methods. An average localization error of about 3.5 mm is obtained for both spherical and realistic head models. Moreover, the ANN localization approach appears to be robust to noise and electrode mislocations. In comparison with the iterative localization, the ANN provides a major speed-up of dipole source localization. We conclude that an artificial neural network is a very suitable alternative for iterative dipole source localization in applications where large numbers of dipole localizations have to be performed, provided that an increase of the localization errors by a few millimetres is acceptable.

An examination is made of dipole location errors in electroencephalogram (EEG) source analysis, due to not incorporating the ventricular system (VS), omitting a hole in the skull and underestimating skull conductivity. The simulations are performed for a large number of test dipoles in 3D using the finite difference method. The maximum dipole location error encountered, utilising 27 and 53 electrodes is 7.6 mm and 6.1 mm, respectively when omitting the VS, 5.6 mm and 5.2 mm, respectively when neglecting the hole in the skull, and 33.4 mm and 28.0 mm, respectively when underestimating skull conductivity. The largest location errors due to neglecting the VS can be found in the vicinity of the VS. The largest location erros due to omitting a hole can be found in the vicinity of the hole. At these positions the fitted dipoles are found close to the hole. When skull conductivity is underestimated, the dipole is fitted close to the skull-brain border in a radial direction for all test dipoles. It was found that the location errors due to underestimating skull conductivity are typically higher than those found due to neglecting the VS or neglecting a hole in the skull.

Measurement noise in the electro-encephalogram (EEG) and inaccurate formation about the locations of the EEG electrodes on the head induce localisation errors in the results of EEG dipole source analysis. These errors are studied by performing dipole source localisation for simulated electrode potentials in a spherical head model, for a range of different dipole locations and for two different numbers (27 and 148) of electrodes. Dipole source localisation is performed by iteratively minimising the residual energy (RE), using the simplex algorithm. The ratio of the dipole localisation error (cm) to the noise level (%) of Gaussian measurement noise amounts to 0.15 cm/% and 0.047 cm/% for the 27 and 148 electrode configurations, respectively, for a radial dipole with 40% eccentricity The localisation error due to noise can be reduced by taking into account multiple time instants of the measured potentials. In the case of random displacements of the EEG electrodes, the ratio of dipole localisation errors to electrode location errors amounts to 0.78 cm−1 cm and 0.27 cm−1 cm for the 27 and 148 electrode configurations, respectively. It is concluded that it is important to reduce the measurement noise, and particularly the electrode mislocalisation, as the influence of the latter is not reduced by taking into account multiple time instants.

In this paper, 51 patients with refractory complex partial seizures (CPS) and intracranial structural abnormalities demonstrated with optimum MR (space-occupying: n = 16; atrophic: n = 32; dysplastic: n = 3) were studied. Video-EEG monitoring showed CPS in all patients. In 13 patients, additional intracranial EEG monitoring demonstrated hippocampal seizure onset in 12 and medial occipital ictal onset in 1 patient. Interictal and ictal dipole modeling using a spherical head model and realistic electrode coordinates were performed. Spatiotemporal dipole mapping of interictal epileptic discharges revealed two distinct dipole patterns. Patients with lesions located in the medial temporal lobe (n = 41) and medial occipital lobe (n = 2) uniformly presented a dipole with an elevation of more than 15 degrees relative to the axial plane. Eight out of ten patients with extratemporal lesions and 1 patient with a pure neocortical temporal lesion had a less stable dipole with an elevation less than 15 degrees relative to the axial plane. Dipole modeling of epochs of early ictal discharges revealed a striking correspondence with the interictal findings in individual patients. Ictal dipole modeling identified the ictal onset zone correctly when compared with intracranial EEG recordings from bilateral hippocampal depth electrodes in patients with medial temporal seizure onset. Mapping of dipoles on MR images of individual patients facilitated clinical interpretation of the EEG data. Interictal and ictal dipole mapping provided additional and clinically relevant information and may obviate the need for intracranial EEG studies in some surgical candidates for refractory CPS.