EEG changes induced by meditative practices: State and trait effects in healthy subjects and in patients with epilepsy.

The effect of meditation on brain activity has been the topic of many studies in healthy subjects and in patients suffering from chronic diseases. These effects are either explored during meditation practice (state effects) or as a longer-term result of meditation training during the resting-state (trait). The topic of this article is to first review these findings by focusing on electroencephalography (EEG) changes in healthy subjects with or without experience in meditation. Modifications in EEG baseline rhythms, functional connectivity and advanced nonlinear parameters are discussed in regard to feasibility in clinical applications. Secondly, we provide a state-of-the-art of studies that proposed meditative practices as a complementary therapy in patients with epilepsy, in whom anxiety and depressive symptoms are prevalent. In these studies, the effects of standardized meditation programs including elements of traditional meditation practices such as mindfulness, loving-kindness and compassion are explored both at the level of psychological functioning and on the occurrence of seizures. Lastly, preliminary results are given regarding our ongoing study, the aim of which is to quantify the effects of a mindfulness self-compassion (MSC) practice on interictal and ictal epileptic activity. Feasibility, difficulties, and prospects of this study are discussed.

Predictive factors of postoperative outcome in the elderly after resective epilepsy surgery.

OBJECTIVE: To evaluate the efficiency of resective epilepsy surgery (RES) in patients over 50 years and determine prognostic factors. RESULTS: Over the 147 patients over 50 years (54.9±3.8 years [50-69]) coming from 8 specialized French centres for epilepsy surgery, 72.1%, patients were seizure-free and 91.2% had a good outcome 12 months after RES. Seizure freedom was not associated with the age at surgery or duration of epilepsy. In multivariate analysis, seizure freedom was associated with MRI and neuropathological hippocampal sclerosis (HS) (P=0.009 and P=0.028 respectively), PET hypometabolism (P=0.013), temporal epilepsy (P=0.01). On the contrary, the need for intracranial exploration was associated with a poorer prognosis (P=0.001). Postoperative number of antiepileptic drugs was significantly lower in the seizure-free group (P=0.001). Neurological adverse event rate after surgery was 21.1% and 11.7% of patients had neuropsychological adverse effects overall transient. CONCLUSIONS: RES is effective procedure in the elderly. Even safe it remains at higher risk of complication and population should be carefully selected. Nevertheless, age should not be considered as a limiting factor, especially when good prognostic factors are identified.

Clinical and biological assessment of lamotrigine and levetiracetam plasma assays at the Rennes University Hospital.

INTRODUCTION: Requests for lamotrigine and levetiracetam plasma assays have increased significantly since their development in the biological and forensic toxicology laboratory at the University Hospital of Rennes in 2015. The purpose of this study was to evaluate the follow-up of French National Authority for Health (HAS) guidelines for antiepileptic drug assays and the impact of assay results on medical management. METHODS: Two hundred and forty-two assay results of these two antiepileptics for 169 patients hospitalized in different care wards between 2015 and 2018 were retrospectively analyzed. RESULTS: The mean age of the study population was 50.3±25.4 years. Of the 207 assays prescribed for epilepsy, 177 (85.5%) were in line with the 2007 HAS guidelines, namely: 76/177 (42.9%) for therapeutic adjustment in the event of seizure recurrence or aggravation; 45/177 (25.4%) for specific clinical situations; 23/177 (13%) for proven or suspected poor compliance; 23/177 (13%) for suspected overdose; 8/177 (4.5%) following initiation of treatment; and 2/177 (1.1%) for drug interaction management. Thirty of the 207 assays (14.5%) were thus inappropriate. No significant differences were found regarding the hospitalization frequency after a visit to the emergency room (P=0.9) between patients with lamotrigine and/or levetiracetam plasma assays in therapeutic ranges versus those with concentrations outside the therapeutic ranges. Dosage changes were more frequent in patients with assays in therapeutic ranges compared to patients with plasma assays outside the therapeutic ranges (P=0.0015), suggesting a treatment reassessment primarily based on clinical criteria. CONCLUSION: The analysis of requests for antiepileptic drug assays at the University Hospital of Rennes revealed that clinicians were well aware of the HAS guidelines. In addition, the assay results were mainly consistent with clinical intuition, suggesting a real added value for patient management. However, the consequences in terms of changes in medical care seem limited. This assessment illustrates the importance of strengthening the dialogue between pharmacists, biologists and clinicians.

[Epidemiology and associated factors with depression among people suffering from epilepsy: A transversal French study in a tertiary center]. / Épidémiologie et facteurs associés au syndrome dépressif chez les patients suivis au centre hospitalo-universitaire de Rennes pour une épilepsie.

OBJECTIVES: The occurrence of depression in people with epilepsy is almost twice as common as in the general population. Furthermore, depression is the first cause of lower quality of life among those patients. Which is why the main goal of this study was to assess the epidemiology of depression and its associated factors among the patients from the tertiary department of epileptology in Rennes. METHODS/RESULTS: The subjects were included prospectively and consecutively at the moment of their consultation or hospitalisation in the department. Personal data about the socio-economic status and the type of epilepsy was collected. The subjects filled validated self-assessment of depression (NDDIE), anxiety (GAD-7) and quality of life (QOLIE-10). Thanks to the NDDIE, the patients were divided into: "depressed" and "not depressed"; and the two groups were compared with univariate and multivariate models. Of the 322 patients followed-up in the department between the 17th of June and the 9th of September 2016 223 of them were included in the study. According to the NDDIE, 22.6% suffered from depression; according to the GAD-7, 46.4% suffered from anxiety. In the "depressed" group, 82% were not under anti-depressant medication. In the univariate model, depression was associated with: anxiety, suicidal ideations, lower quality of life, vague nervus stimulation treatment, anticonvulsant benzodiazepine medication or psychiatric medication, and last of all bitherapy or polytherapy antiepileptic medication compared to monotherapy. In the multivariate model, depression was significantly related to anxiety (OR: 8.86 [3.00; 26.19] p=0.0001), suicidal ideas (OR: 7.43 [2.93; 18.81] p<0.0001), anticonvulsant benzodiazepine medication (OR: 3.31 [1.16; 9.49] p=0.0255), and lower quality of life (OR: 1.09 [1.02; 1.17] p=0.0087). Generalised epilepsy was a protective factor with uni and multivariate models (OR: 0.34 [0.11; 1.00] p=0.0492). CONCLUSIONS: In the tertiary epileptic department of Rennes, more than 20% of patients with epilepsy suffered from depression during the inclusion period according to the NDDIE. Among those "depressed" subjects, fewer than one out of five seemed to receive proper psychiatric care. Which is why this study highlights the importance of interdisciplinary cooperation between neurologists and psychiatrists in order to aim at better management of epileptic patients as a whole.

Complex patterns of spatially extended generators of epileptic activity: Comparison of source localization methods cMEM and 4-ExSo-MUSIC on high resolution EEG and MEG data.

Electric Source Imaging (ESI) and Magnetic Source Imaging (MSI) of EEG and MEG signals are widely used to determine the origin of interictal epileptic discharges during the pre-surgical evaluation of patients with epilepsy. Epileptic discharges are detectable on EEG/MEG scalp recordings only when associated with a spatially extended cortical generator of several square centimeters, therefore it is essential to assess the ability of source localization methods to recover such spatial extent. In this study we evaluated two source localization methods that have been developed for localizing spatially extended sources using EEG/MEG data: coherent Maximum Entropy on the Mean (cMEM) and 4th order Extended Source Multiple Signal Classification (4-ExSo-MUSIC). In order to propose a fair comparison of the performances of the two methods in MEG versus EEG, this study considered realistic simulations of simultaneous EEG/MEG acquisitions taking into account an equivalent number of channels in EEG (257 electrodes) and MEG (275 sensors), involving a biophysical computational neural mass model of neuronal discharges and realistically shaped head models. cMEM and 4-ExSo-MUSIC were evaluated for their sensitivity to localize complex patterns of epileptic discharges which includes (a) different locations and spatial extents of multiple synchronous sources, and (b) propagation patterns exhibited by epileptic discharges. Performance of the source localization methods was assessed using a detection accuracy index (Area Under receiver operating characteristic Curve, AUC) and a Spatial Dispersion (SD) metric. Finally, we also presented two examples illustrating the performance of cMEM and 4-ExSo-MUSIC on clinical data recorded using high resolution EEG and MEG. When simulating single sources at different locations, both 4-ExSo-MUSIC and cMEM exhibited excellent performance (median AUC significantly larger than 0.8 for EEG and MEG), whereas, only for EEG, 4-ExSo-MUSIC showed significantly larger AUC values than cMEM. On the other hand, cMEM showed significantly lower SD values than 4-ExSo-MUSIC for both EEG and MEG. When assessing the impact of the source spatial extent, both methods provided consistent and reliable detection accuracy for a wide range of source spatial extents (source sizes ranging from 3 to 20cm2 for MEG and 3 to 30cm2 for EEG). For both EEG and MEG, 4-ExSo-MUSIC localized single source of large signal-to-noise ratio better than cMEM. In the presence of two synchronous sources, cMEM was able to distinguish well the two sources (their location and spatial extent), while 4-ExSo-MUSIC only retrieved one of them. cMEM was able to detect the spatio-temporal propagation patterns of two synchronous activities while 4-ExSo-MUSIC favored the strongest source activity. Overall, in the context of localizing sources of epileptic discharges from EEG and MEG data, 4-ExSo-MUSIC and cMEM were found accurately sensitive to the location and spatial extent of the sources, with some complementarities. Therefore, they are both eligible for application on clinical data.

HD-EEG for tracking sub-second brain dynamics during cognitive tasks.

This work provides the community with high-density Electroencephalography (HD-EEG, 256 channels) datasets collected during task-free and task-related paradigms. It includes forty-three healthy participants performing visual naming and spelling tasks, visual and auditory naming tasks and a visual working memory task in addition to resting state. The HD-EEG data are furnished in the Brain Imaging Data Structure (BIDS) format. These datasets can be used to (i) track brain networks dynamics and their rapid reconfigurations at sub-second time scale in different conditions, (naming/spelling/rest) and modalities, (auditory/visual) and compare them to each other, (ii) validate several parameters involved in the methods used to estimate cortical brain networks through scalp EEG, such as the open question of optimal number of channels and number of regions of interest and (iii) allow the reproducibility of results obtained so far using HD-EEG. We hope that delivering these datasets will lead to the development of new methods that can be used to estimate brain cortical networks and to better understand the general functioning of the brain during rest and task. Data are freely available from https://openneuro.org .

Chronic vagus nerve stimulation decreased weight gain, food consumption and sweet craving in adult obese minipigs.

Chronic vagus nerve stimulation (VNS) is known to influence food intake and body weight in animals and humans. The aim of our work was to evaluate the effects of long-term VNS in adult obese minipigs. Eight minipigs were fed ad libitum a Western diet to cause obesity, after which half of the animals were implanted with bilateral vagal electrodes connected to constant current stimulators (2mA, 30Hz, 500-µs pulse, ON 30s, OFF 5min). The other animals were implanted with sham devices. Animals were weighed weekly and their daily consumption was measured. Still 14 weeks after surgery, VNS animals (70.3±3.3kg, P>0.10) did not significantly gain weight compared to sham animals (80.6±8.0kg, P<0.05). Furthermore, food consumption decreased in VNS animals (-18%, P<0.02) compared to sham animals (+1%, P>0.10). When subjected to a three-choice meal test (high-fat vs. high-carbohydrates vs. balanced diet), VNS animals decreased their sweet-food consumption compared to sham animals (P<0.05), and increased their balanced diet consumption in comparison to pre-surgery levels. Our results showed that chronic VNS decreased weight gain, food consumption and sweet craving in adult obese minipigs, which indicates that this therapy might be used to decrease appetite in the context of morbid obesity.

[On the best strategies on the best results for surgery of frontal epilepsy]. / Quelles stratégies pour quels résultats dans la chirurgie des épilepsies partielles frontales?

Frontal lobe epilepsy surgery is the second most common surgery performed for drug-resistant partial epilepsy. We investigated the longitudinal outcome in a cohort of patients investigated since 1990 with SEEG and modern diagnostic techniques. We reviewed 105 patients who underwent surgery between 1990 and 2005 (mean follow-up, six years; range: one to 17 years) and analyzed the year-per-year follow-up according to Engel's classification. Favorable outcome (Class I) was observed for 70% and this result was stable at least five years after surgery. More than 90% of patients with lesion-related epilepsies (focal cortical dysplasia and dysembryoplastic neuroepithelial tumors) became seizure-free. Less than 50% of patients classified as having cryptogenic epilepsy (defined as normal imaging and neuropathology on surgical specimen) had a favorable outcome. Permanent neurological sequelae were subtle and rare, especially after surgery for dysplasia in eloquent cortex (primary motor cortex). Our data indicate that frontal surgery is a successful treatment in patients when electrophysiological and morphological investigations demonstrate a well-defined epileptogenic zone or lesion to be surgically resected. Progress in electrophysiological and brain-imaging techniques will further improve the selection of frontal lobe epilepsy surgery candidates.

[Medicoeconomic assessment of epilepsy surgery in adults with medically intractable partial epilepsy. Three-year outcomes from a multicenter French cohort]. / Evaluation médicoéconomique de la chirurgie des épilepsies partielles pharmacorésistantes de l'adulte. Résultats à trois ans d'une étude prospective multicentrique française.

PURPOSE: To compare resective surgery and medical therapy in a cost-effectiveness analysis in a multicenter cohort of adult patients with partial intractable epilepsy. POPULATION AND METHODS: Adult patients with partial, medically intractable, potentially operable epilepsy were eligible and followed every year over five years. Effectiveness was defined as one year without seizure. The long-term costs and effectiveness were extrapolated over the patients' lifetime with a Markov model. Productivity (indirect costs) and quality of life (QOLIE-31, SEALS) were also assessed. Changes before and after surgery were compared between the two groups. RESULTS: Two hundred and eighty-nine patients were included (119 with surgery, 161 medically treated, six not eligible, three lost to follow-up). One year after surgery, 81% of the patients were seizure-free; at two and three years, this rate was 78%. In the medical group, these rates were 10, 18, and 15%, respectively. The cost of the explorations was euro 8464; including surgery, it was euro 19,700. In the medical group, the average annual direct costs were between 3500 and euro 6000. At two years after surgery, the annual direct cost decreased to euro 2768, at three years, it was euro 1233, predominately antiepileptic drug costs. Surgery became cost-effective between seven and eight years. In the surgical group, all the quality-of-life scores improved at one year after surgery and were stable during the second and third years. CONCLUSION: Surgical therapy was cost-effective at the middle term even though indirect costs were not considered.

[Use of generic anti-epilepsy drugs in France: survey of neurologists and review of the literature]. / Utilisation des médicaments génériques des anti-épileptiques en France: résultats d'une enquête auprès des neurologues et revue de la littérature.

INTRODUCTION: The use of generic substitution for antiepileptic drugs is more and more frequent but remains controversial. PURPOSE AND METHODS: This survey aimed to assess physicians' feelings towards effectiveness, tolerability and clinical impact of generic substitution of antiepileptic drugs on their patients. A questionnaire was sent to all French private neurologists and hospital specialists in epilepsy. Their responses were recorded from December 2005 to March 2006. RESULTS: A total of 312 neurologists responded. A few prescribed generic antiepileptic drugs; but a few as well indicated not to switch their prescription. Most of them felt discomfort by generic substitution. One third reported breakthrough seizures or new adverse events after generic substitution and 70p.cent extra phone consultation. DISCUSSION: Neurologists' reluctance with prescribing generic AEDs may be explained by several different facts: no controlled study about the safety and efficacy of generic AEDs as compared with brand name drugs, substitutions by pharmacists without their agreement, lack of medical information about generic AEDs, symbolic dimension of the treatment, and, most of all, the fear of breakthrough seizures in patients good controlled. CONCLUSION: A prospective controlled evaluation of the safety and efficacy of generic substitution in epilepsy needs to be performed.

[Vagal nerve stimulation as a treatment of epilepsy]. / La stimulation du nerf vague dans le traitement de l'épilepsie.

INTRODUCTION: Vagus nerve stimulation (VNS) is a non-pharmacological treatment for drug resistant epilepsy. STATE OF ART: The good efficacy and tolerability of this device is now well established after several controlled studies, and more than 17000 people operated on in different countries. The physiology of VNS is not yet well known, and the potential mechanisms of action are reviewed. VNS seems to be as efficient as a new medication without some of the disadvantages (in case of pregnancy for example). SNV may have a beneficial effect for all kinds of drug-resistant epilepsy. PERSPECTIVES: Better knowledge of the underlying anti-epileptic mechanisms may help to select the better responders to this expensive anti-epileptic tool.

Identification of epileptogenic networks from dense EEG: A model-based study.

Epilepsy is a network disease. Identifying the epileptogenic networks from noninvasive recordings is a challenging issue. In this context, M/EEG source connectivity is a promising tool to identify brain networks with high temporal and spatial resolution. In this paper, we analyze the impact of the two main factors that intervene in EEG source connectivity processing: i) the algorithm used to solve the EEG inverse problem and ii) the method used to measure the functional connectivity. We evaluate three inverse solutions algorithms (dSPM, wMNE and cMEM) and three connectivity measures (r(2), h(2) and MI) on data simulated from a combined biophysical/physiological model able to generate realistic interictal epileptic spikes reflected in scalp EEG. The performance criterion used here is the similarity between the network identified by each of the inverse/connectivity combination and the original network used in the source model. Results show that the choice of the combination has a high impact on the identified network. Results suggest also that nonlinear methods (nonlinear correlation coefficient and mutual information) for measuring the connectivity are more efficient than the linear one (the cross correlation coefficient). The dSPM as inverse solution shows the lowest performance compared to cMEM and wMNE.

Ictal cerebral blood flow in seizures originating in the posterolateral cortex.

UNLABELLED: In selecting patients for epilepsy surgery, it is important to distinguish mesial temporal seizures from seizures originating in the posterolateral cortex. We studied ictal cerebral perfusion in five patients with complex partial seizures with clear posterior EEG ictal onsets and clinical seizures semiology suggesting seizure origin in the posterolateral cortex. METHODS: Ictal SPECT was performed during video EEG monitoring using 99mTc-HMPAO as a cerebral perfusion tracer and a rotating gamma camera to acquire images. RESULTS: Three patterns of ictal hyperperfusion were seen: pattern A = temporoparieto-occipital junction extending into the lateral temporal cortex, involving the mesial temporal cortex and basal ganglia to a lesser degree and a small area of hyperperfusion in the contralateral parietal cortex (two patients); pattern B = pattern A but with no hyperperfusion of the mesial temporal cortex (one patient); and pattern C = localized hyperperfusion in the area of the temporoparieto-occipital junction (two patients). CONCLUSION: Our results suggest distinct patterns of ictal perfusion in seizures with posterolateral ictal EEG onsets. Ictal SPECT may be useful in distinguishing such seizures.

Altered patterns of catecholaminergic fibers in focal cortical dysplasia in two patients with partial seizures.

We present the histologic study of two patients who underwent cerebral cortex resection for partial seizures linked with cortical dysplasia. The distinction of areas of seizure origin from areas of seizure propagation was made according to stereoelectroencephalographic criteria. Samples of epileptogenic tissue were studied by using cytoarchitectonic and immunohistochemical stainings. We mapped the catecholaminergic afferents by employing antisera directed against tyrosine hydroxylase and dopamine-beta-hydroxylase enzymes. The epileptic activity was correlated with the underlying patterns of cytoarchitectonic and immunohistochemical changes. The neuropathological features were focal and consisted of large neurons dispersed through all but the first cortical layer (associated in one case to giant glial cells), of variable disturbance of lamination, of neuronal ectopia in the white matter and of moderate proliferation of small glial cells. Areas of seizure onset coincided with that of dysplastic zones. Both laminar distribution and density of catecholaminergic fibers were altered in the dysplastic cortices (area of seizure onset) and there was an increase in the density of tyrosine hydroxylase-immunoreactive fibers in the surrounding areas of seizure propagation. Our results indicate that these developmental epileptogenic lesions were associated with abnormal neuronal circuitry. They provide evidence at the structural level of the increase in tyrosine hydroxylase activity previously reported in spiking areas of human epileptogenic cerebral cortex and they suggest that catecholamines may contribute toward limiting seizure activity propagation.

A methodology for generating normal and pathological brain perfusion SPECT images for evaluation of MRI/SPECT fusion methods: application in epilepsy.

Quantitative evaluation of brain MRI/SPECT fusion methods for normal and in particular pathological datasets is difficult, due to the frequent lack of relevant ground truth. We propose a methodology to generate MRI and SPECT datasets dedicated to the evaluation of MRI/SPECT fusion methods and illustrate the method when dealing with ictal SPECT. The method consists in generating normal or pathological SPECT data perfectly aligned with a high-resolution 3D T1-weighted MRI using realistic Monte Carlo simulations that closely reproduce the response of a SPECT imaging system. Anatomical input data for the SPECT simulations are obtained from this 3D T1-weighted MRI, while functional input data result from an inter-individual analysis of anatomically standardized SPECT data. The method makes it possible to control the 'brain perfusion' function by proposing a theoretical model of brain perfusion from measurements performed on real SPECT images. Our method provides an absolute gold standard for assessing MRI/SPECT registration method accuracy since, by construction, the SPECT data are perfectly registered with the MRI data. The proposed methodology has been applied to create a theoretical model of normal brain perfusion and ictal brain perfusion characteristic of mesial temporal lobe epilepsy. To approach realistic and unbiased perfusion models, real SPECT data were corrected for uniform attenuation, scatter and partial volume effect. An anatomic standardization was used to account for anatomic variability between subjects. Realistic simulations of normal and ictal SPECT deduced from these perfusion models are presented. The comparison of real and simulated SPECT images showed relative differences in regional activity concentration of less than 20% in most anatomical structures, for both normal and ictal data, suggesting realistic models of perfusion distributions for evaluation purposes. Inter-hemispheric asymmetry coefficients measured on simulated data were found within the range of asymmetry coefficients measured on corresponding real data. The features of the proposed approach are compared with those of other methods previously described to obtain datasets appropriate for the assessment of fusion methods.

Influence of the critical EEG pattern on blood flow variations measured by single photon computed emission tomography.

Anatomo-electro-clinical correlation's using stereo-electro-encephalography (SEEG) or electro-cortico-graphy (EcoG) are the gold standard for delineating the epileptic zone (EZ) in patients with partial epilepsy. These two techniques reflect the temporal and spatial dimensions of the epileptic fit. More recently, ictal Single Photon Computed Tomography (SPECT) compared with interictal SPECT allows anatomo-clinical correlations. SPECT reflects variations of the regional cerebral blood flow (rCBF) during the seizure. These variations of the rCBF are linked with the electrical activity but the relations between electrical activity and rCBF have not been well studied and it is still difficult to compare ictal/interictal SPECT with the SEEG and EcoG data to delineate the EZ. From the few published studies, we know that, if the injection of the SPECT tracer is performed at the onset of the seizure, while the fast ictal discharge is still going on, we shall observe a local hyperperfusion in the region where the discharge started and in the region where it propagated secondarily. If the tracer injection is performed late during the seizure, or after the end of it, we shall observe a local hypoperfusion in these regions, this has also a good localizing value. Time of injection must be known, as it represents a key issue for SPECT interpretation.

Gelastic seizures: video-EEG and scintigraphic analysis of a case with a frontal focus; review of the literature and pathophysiological hypotheses.

We report scalp EEG and SPECT findings in a young patient who experienced gelastic seizures; clinical, EEG and scintigraphic data strongly suggested a frontal focus in a context of cryptogenic epilepsy. Few cases of gelastic seizures originating in the frontal lobe have been reported in the literature, most of them involving a diencephalic hamartoma or a temporal focus although, no clinical pattern has been found to be specific for each of these three anatomical regions. The ictal laughter is of variable nature, unmotivated or associated with feelings of mirth, forced or natural, except in the case of a frontal focus where the laughter seems consistently described as forced and unmotivated. However, mirth and laughter are two dissociable clinical elements; their genesis probably involves distinct mechanisms. Anatomical considerations lead to several hypotheses concerning laughter generation: it could be a simple reactional behavior in response to a modified cognitive process, an automatic behavior or a forced action. In a few cases with a temporal focus, laughter seems directly related to a disorganization of the associative temporal cortex and may be considered as a reactional behavior. In cases with frontal focus, anterior cingulate and orbital structures would be particularly implicated in laughter genesis, although with possible different pathophysiological routes: in the first case by disconnection within the premotor mesial system or by an imbalance between premotor mesial and premotor lateral systems, and in the second case by activation of a previously conditioned orbital region.

Video-EEG and ictal SPECT in three patients with both epileptic and non-epileptic seizures.

We report scalp EEG and ictal SPECT findings in epileptic (complex partial) and non-epileptic seizures in three patients who experienced both types of event during presurgical investigation of medically intractable epilepsies. In all three patients, ictal SPECT showed localizing changes in cerebral blood flow during epileptic seizures, but showed no change during pseudoseizures. In two patients, the physical manifestations of the pseudoseizures were similar to those of the epileptic seizures, supporting the contention that physiological activation is unlikely to mimic ictal perfusion changes. In one patient, the EEG recording was rendered difficult to interpret by muscle artefact, while SPECT was clear and showed no change. SPECT is not a primary tool for diagnosis of pseudoseizures, but when patients undergoing presurgical investigation are injected during pseudoseizures, then SPECT is unlikely to show misleading perfusion changes due to activation effects, and may aid diagnosis where there is muscle artefact on EEG.

Comparison of twice- and three times daily tiagabine for the adjunctive treatment of partial seizures in refractory patients with epilepsy: an open label, randomised, parallel-group study.

UNLABELLED: A multicentre, open label, randomised, parallel group study compared the efficacy, tolerability and safety of two dosing regimens, t.i.d. and b.i.d., of tiagabine as an adjunctive therapy for the treatment of refractory patients with partial seizures. A total of 347 patients were randomised and treated (175 t.i.d. and 172 b.i.d.). Each group was administered the same daily dose of tiagabine incremented stepwise during a 12-week fixed-schedule titration period to a target dose of 40 mg/day. The patients were followed for a further 12-week flexible continuation phase. A significantly greater number of patients in the t.i.d. group completed the fixed schedule titration period (81.4% versus 73.1%; 95% CI of odds ratio = 0.331, 0.970; p = 0.038). The proportion of responders (patients showing at least a 50% decrease in all-seizure frequency from baseline) was similar for both groups (42.3% for b.i.d. and 47.1% for t.i.d.) during the last 8 weeks of the flexible phase and seven (4.0%) patients in the b.i.d. group were seizure-free compared to 14 (8.1%) patients in the t.i.d. group. Adverse events were of similar incidence in both groups, and mainly occurred during the fixed schedule titration period; they were mainly mild and CNS-related with somnolence being the most frequently reported. CONCLUSION: Tiagabine was effective as add-on treatment of refractory partial seizures. Although both regimens appear to offer a similar efficacy and safety profile, significantly more patients completed the study in the t.i.d. group compared to b.i.d., probably as a consequence of a lesser tolerability when high doses are given undivided. These results confirm that a slow titration and appropriate adjustment of dosing are essential conditions to ensure optimal use of tiagabine.

[Use of topiramate in clinical practice (part 2). Multicentric retrospective evaluation of its safety]. / Utilisation pratique du topiramate (2e partie). Analyse rétrospective multicentrique de sa sécurité d'emploi.

Randomized, controlled studies of new antiepileptic drugs are carried out following strict rules and do not always predict the drug's tolerability in clinical practice. The authors gathered 361 cases of focal epilepsies treated with topiramate (TPM) as an add-on to other antiepileptic drugs prior to marketing, in order to retrospectively analyze the incidence of adverse effects (AE). These patients had been treated by neurologists in a clinical setting, with free choice of associated drugs, titration and final daily dose. Compared with controlled studies, TPM was titrated slowly (mean rate: 43 mg/week, vs 100-200), and was given at a lower final dose (296 mg/d, vs 200 to 1000). This analysis shows that AE were less frequent and that TPM had an original tolerability profile, with CNS-related AE, often combined in the same patient (somnolence: 16. 1p.100, fatigue: 11.9p.100, mental slowing: 9.1p.100, slurred speech: 2,2p.100), and weight loss (14.7p.100 of patients, mean 4.5 kg or 6.6p.100 of body weight). Severe AE were uncommon (psychosis, 1; skin rash, 2; urinary lithiasis, 2). Withdrawal of TPM was caused by AE (13.6p.100), lack of efficacy (8.3p.100), aggravation of epilepsy (6.1p.100) or by a combination of these (5p.100). It is useful to use slow titration, in order to allow the greatest possible number of patients to benefit from its efficacy as an add-on drug in the treatment of resistant focal epilepsies.