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Michel Baulac

Publications and source records attributed to Michel Baulac.

35 records · Page 2Linked to original sources

Preictal state identification by synchronization changes in long-term intracranial EEG recordings.

OBJECTIVE: There is accumulated evidence that mesial temporal lobe seizures are preceded by a preictal transition that evolves over minutes to hours. In the present study, we investigated these possible preictal changes in long-term intracranial recordings of five patients by a measure of phase synchronization. In order to clearly distinguish preictal changes from all the other interictal states, we developed an automatic extraction of representative patterns of interictal synchronization activity. This reference library was used to classify the successive synchronization patterns of long-term recordings into groups of similar patterns. Altered states of brain synchronization were identified as deviating from patterns in the reference library and were evaluated relative to the times of seizure onset in terms of sensitivity and specificity. METHODS: A phase-locking measure was estimated using a sliding window analysis on 15 frequency bands (2Hz steps between 0 and 30Hz), for all pairs of EEG channels in the epileptogenic temporal lobe (14-20 channels), over the entire data sets (total analyzed duration 305h). The preictal identification encompasses three basic stages: (1) a preprocessing stage involving the determination of a reference library of characteristic interictal synchronization patterns using a K-means algorithm, and the identification of discriminant variables differentiating interictal from preictal states, (2) a classification stage of the synchronization pattern via a minimum Mahalanobis distance to the reference patterns, as well as detection of outliers, (3) an evaluation stage of the sensitivity and specificity of the detection by receiver-operating characteristic curves. RESULTS: In most of the cases (36 of 52 seizures, i.e. 70%), a specific state of brain synchronization can be observed several hours before the actual seizure. The changes involved both increases and decreases of the synchronization levels, occurring mostly within the 4-15Hz frequency band, and were often localized near the primary epileptogenic zone. CONCLUSIONS: The analysis of phase synchronization offers a way to distinguish between a preictal state and normal interictal activity. These findings suggest that brain synchronizations are preictally altered in the epileptogenic temporal lobe, inducing a pathological state of higher susceptibility for seizure activity. SIGNIFICANCE: Phase synchronization is capable of extracting information from the EEG that allow the definition of a preictal state. Although the proposed analysis does not constitute genuine seizure anticipation, these changes in neuronal synchronization may provide helpful information for prospective seizure warning.

Brain Mapping↗

Productive and perceptive language reorganization in temporal lobe epilepsy.

The aim of this work was to determine whether productive and perceptive language functions are differentially affected in homogeneous groups of epilepsy patients with right and left temporal lobe epilepsy (TLE). Eighteen patients with left TLE, 18 with right TLE, and 17 healthy volunteers were studied using fMRI during performance of three tasks assessing the productive and perceptive aspects of language (covert semantic verbal fluency, covert sentence repetition, and story listening). Hemispheric dominance for language was calculated in the frontal and temporal regions using laterality indices (LI). Atypical lateralization was defined as a right-sided LI (LI<-0.20) in the frontal lobes during the verbal fluency task or in the temporal lobes during the story listening task. Control subjects and right TLE patients demonstrated a strong left lateralization for language in the frontal lobes during the fluency task, whereas activation was less lateralized to the left hemisphere in left TLE patients, although the difference did not reach significance. In the story listening and the repetition tasks, activation was significantly more right sided in the temporal lobes of patients with left TLE. Atypical language representation was found in 19% of TLE patients (five left and two right TLE). The shift toward the right hemisphere was significantly larger in the temporal than the frontal lobes in patients with atypical language lateralization compared to TLE patients with a typical language lateralization. Neuropsychological performances of patients with atypical language patterns were better than those of patients with typical patterns, suggesting that this reorganization may represent a compensatory mechanism.

Adolescent↗

Monogenic idiopathic epilepsies.

Major advances have recently been made in our understanding of the genetic bases of monogenic inherited epilepsies. Direct molecular diagnosis is now possible in numerous inherited symptomatic epilepsies. Progress has also been spectacular with respect to several idiopathic epilepsies that are caused by mutations in genes encoding subunits of ion channels or neurotransmitter receptors. Although these findings concern only a few families and sporadic cases, their potential importance is great, because these genes are implicated in a wide range of more common epileptic disorders and seizure types as well as some rare syndromes. Functional studies of these mutations, while leading to further progress in the neurobiology of the epilepsies, will help to refine genotype-phenotype relations and increase our understanding of responses to antiepileptic drugs. In this article, we review the clinical and genetic data on most of the idiopathic human epilepsies and epileptic contexts in which the association of epilepsy and febrile convulsions is genetically determined.

Animals↗

Fever, genes, and epilepsy.

About 13% of patients with epilepsy have a history of febrile seizures (FS). Studies of familial forms suggest a genetic component to the epidemiological link. Indeed, in certain monogenic forms of FS, for which several loci have been reported, some patients develop epilepsy with a higher risk than in the general population. Patients with generalised epilepsy with febrile seizures plus (GEFS+) can have typical and isolated FS, FS lasting more beyond age 6 years, and subsequent afebrile (typically generalised) seizures. Mutations associated with GEFS+ were identified in genes for subunits of the voltage-gated sodium channel and the gamma2 subunit of the ligand-gated GABAA receptor. Screening for these genes in patients with severe myoclonic epilepsy in infancy showed de novo mutations of the alpha1 subunit of the voltage-gated sodium channel. Antecedent FS are commonly observed in temporal-lobe epilepsy (TLE). In sporadic mesial TLE-characterised by the sequence of complex FS in childhood, hippocampal sclerosis, and refractory temporal-lobe seizures-association studies suggested the role of several susceptibility genes. Work on some large pedigrees also suggests that FS and temporal-lobe seizures may have a common genetic basis, whether hippocampus sclerosis is present or not. The molecular defects identified in the genetic associations of FS and epileptic seizures are very attractive models to aid our understanding of epileptogenesis and susceptibility to seizure-provoking factors, especially fever.

Epilepsy↗

[Place of surgery in the treatment of adult temporal lobe epilepsy].

Surgery for temporal lobe epilepsy has made significant progress during the past twenty years: in addition to traditional factors (frequency of partial seizures and relative resistance to medical treatment), the possibilities offered by MRI in a large number of cases to detect the responsible lesion (hippocampal sclerosis in the majority of cases) has led to an increase in the use of surgical methods. Furthermore, other examinations (EEG-video, SPECT Depth-electrode recording) now permit precise localization of the epileptic focus. Surgical techniques have likewise been considerably modified: in parallel to classical temporal lobectomy, new surgical methods offer more restricted resection of the lateral cortex. The results are, on the whole, quite satisfactory, as three-quarters of patients can be considered cured or greatly improved. The length of post-operative follow-up does not seem to influence the quality of the results, as observed by the end of the second year.

Electroencephalography↗

Spatial and non-spatial auditory short-term memory in patients with temporal-lobe lesion.

Primate auditory systems are divided into at least two different pathways. One refers to objects and the other deals with localization. To investigate auditory spatial and non-spatial short-term memory, we tested patients with unilateral medial temporal lobe lesions including the pole in two tasks involving either sound localization discrimination or auditory object discrimination. The results showed that both left and right temporal lobe lesions impaired spatial short-term memory whereas only lesions on the right affected non-spatial short-term memory. By contrast, the same patients were able to perform the tasks when short interstimulus intervals were used suggesting that short-term memory deficits can not be ascribed to difficulties in perception. These findings document, for the first time, in a neurological population, the functional dissociation between spatial and non-spatial auditory short-term memory that seem to depend on separate neural circuits within the medial temporal lobe.

Acoustic Stimulation↗

Spatio-temporal dynamics prior to neocortical seizures: amplitude versus phase couplings.

The mechanisms underlying the transition of brain activity toward epileptic seizures remain unclear. Based on nonlinear analysis of both intracranial and scalp electroencephalographic (EEG) recordings, different research groups have recently reported dynamical smooth changes in epileptic brain activity several minutes before seizure onset. Such preictal states have been detected in populations of patients with mesial temporal lobe epilepsy (MTLE) and, more recently, with different neocortical partial epilepsies (NPEs). In this paper, we are particularly interested in the spatio-temporal organization of epileptogenic networks prior to seizures in neocortical epilepsies. For this, we characterize the network of two patients with NPE by means of two nonlinear measures of interdependencies. Since the synchronization of neuronal activity is an essential feature of the generation and propagation of epileptic activity, we have analyzed changes in phase synchrony between EEG time series. In order to compare the phase and amplitude dynamics, we have also studied the degree of association between pairs of signals by means of a nonlinear correlation coefficient. Recent findings have suggested changes prior to seizures in a wideband frequency range. Instead, for the examples of this study, we report a significant decrease of synchrony in the focal area several minutes before seizures (>>30 min in both patients) in the frequency band of 10-25 Hz mainly. Furthermore, the spatio-temporal organization of this preictal activity seems to be specifically related to this frequency band. Measures of both amplitude and phase coupling yielded similar results in narrow-band analysis. These results may open new perspectives on the mechanisms of seizure emergence as well as the organization of neocortical epileptogenic networks. The possibility of forecasting the onset of seizures has important implications for a better understanding, diagnosis and a potential treatment of the epilepsy.

Adult↗

Toward a neurodynamical understanding of ictogenesis.

Although considerable information on cellular and network mechanisms of epilepsy exists, it is still not understood why, how, and when the transition from interictal to ictal state takes place. The authors review their work on nonlinear EEG analysis and provide consistent evidences that dynamical changes in the neural activity allows the characterization of a preictal state several minutes before seizure onset. This new neurodynamical approach of ictogenesis opens new perspectives for studying the basic mechanisms in epilepsy as well as for possible therapeutic interventions.

Brain↗

Effect of unilateral temporal lobe resection on short-term memory for auditory object and sound location.

To investigate auditory spatial and nonspatial short-term memory, a sound location discrimination task and an auditory object discrimination task were used in patients with medial temporal lobe resection. The results showed a double dissociation between the side of the medial temporal lobe lesion and the nature of the auditory discrimination deficits, suggesting that right and left temporal lobe structures are differently involved in auditory spatial and nonspatial short-term memory.

Acoustic Stimulation↗

Rational conversion from antiepileptic polytherapy to monotherapy.

For patients with epilepsy, the goal of treatment is to achieve seizure freedom with minimal or no adverse events. Around 60%-70% of newly diagnosed patients will achieve this goal with single antiepileptic drug (AED) therapy, and there is universal agreement that prescription of a single agent constitutes best practice for such patients. For the 30%-40% of patients with poorly controlled epilepsy, treatment options are less clear and many receive add-on therapy with one or more AEDs in an attempt to improve seizure control. Because the therapeutic gain from adjunctive therapy is often marginal and may be complicated by increased drug toxicity, converting individual patients from polytherapy to monotherapy is a common clinical problem facing physicians managing patients with epilepsy today. Evidence from studies with both standard and new AEDs shows that selected patients, including those with previously resistant epilepsy, can be converted successfully from polytherapy to monotherapy without loss of seizure control and in some cases with improved seizure control. Adverse effects can be minimised during the conversion process by slow withdrawal of the first prescribed drug, while increasing the daily dose of the add-on AED to achieve optimal therapeutic doses/levels for continued monotherapy. Deciding which drug(s) to withdraw and which to continue as monotherapy requires adequate consideration of individual patient needs with reference to clinical profiles (seizure type and severity), previous response to individual AEDs and the pharmacokinetic and pharmacodynamic implications of withdrawal.

Anticonvulsants↗

Temporal pole hypometabolism may be linked to a reduction of grey matter in temporal lobe epilepsy.

In order to gain further insight into the pathophysiology of temporal pole hypometabolism, we decided to perform a voxel-based automated analysis of structural MRI in epileptic patients with or without temporal pole hypometabolism. After fully automated segmentation of cerebral grey matter from structural T1-weighted MRI scans, we applied the automated technique of statistical parametric mapping (SPM) to the analysis of grey matter of nine control subjects, and 18 patients with right medial temporal lobe epilepsy with (n = 13) or without (n = 5) significant temporal pole hypometabolism. Group comparisons between subject controls and epileptic patients with temporal pole hypometabolism showed a reduction of grey matter located into the superior part of the right temporal pole, the right hippocampus and the left parahippocampal gyrus. Epileptic patients without temporal pole hypometabolism did not exhibit temporal pole grey matter abnormalities. These findings suggest that a reduction of temporal pole neocortical grey matter might contribute to temporal pole hypometabolism in temporal lobe epilepsy.

Adult↗

On the origin of interictal activity in human temporal lobe epilepsy in vitro.

The origin and mechanisms of human interictal epileptic discharges remain unclear. Here, we describe a spontaneous, rhythmic activity initiated in the subiculum of slices from patients with temporal lobe epilepsy. Synchronous events were similar to interictal discharges of patient electroencephalograms. They were suppressed by antagonists of either glutamatergic or gamma-aminobutyric acid (GABA)-ergic signaling. The network of neurons discharging during population events comprises both subicular interneurons and a subgroup of pyramidal cells. In these pyramidal cells, GABAergic synaptic events reversed at depolarized potentials. Depolarizing GABAergic responses in neurons downstream to the sclerotic CA1 region contribute to human interictal activity.

Action Potentials↗

Insular cortex involvement in mesiotemporal lobe epilepsy: a positron emission tomography study.

Somesthetic and emotional symptoms that are common in patients with mesial temporal lobe epilepsy are usually related to hippocampo-amygdalar complex involvement. Recent stereo-electroencephalographic studies have shown a relationship between such symptoms and epileptic insular discharges. To further investigate this problem, we carried out a positron emission tomography study using fluorodeoxyglucose (18F-FDG) and flumazenil (11C-FMZ) in mesial temporal lobe epilepsy patients. The aim of our study was to assess the existence of a cortical insular involvement in order to examine its clinical correlates and the relationship between the postoperative outcome and the insular involvement. Fluorodeoxyglucose and flumazenil-positron emission tomography studies were carried out in 18 patients with mesial temporal lobe epilepsy patients. A statistical parametric mapping (SPM96) was performed to analyze the data in comparison to 18 healthy volunteers. For each set of fluorodeoxyglucose and flumazenil images a group and an individual analysis were performed. In addition, a region of interest analysis was performed to validate the results. Focusing on the metabolic abnormalities, we also investigated the role of insular cortex in the symptoms experienced by the patients and the prognostic value of insular metabolic abnormalities. Highly significant hypometabolism and BZR binding decreases were detected in the insular cortex. Results were similar using the region of interest approach. Insular involvement (mainly ipsilateral to the seizure focus) was present in 60% of the patients. Emotional symptoms correlated with hypometabolism in the anterior part of the ipsilateral insular cortex, whereas somesthetic symptoms correlated with hypometabolism in the posterior part. No relationship between postoperative outcome and ipsilateral insular hypometabolism was found. Unilateral mesial temporal lobe epilepsy is associated with insular hypometabolism and benzodiazepine receptor loss. Our results also suggest that the anterior part of the insular cortex is involved in the emotional symptoms and the posterior insular cortex is involved in the somesthetic symptoms. Hypometabolism located in the insula did not influence postoperative outcome after anterior lobectomy.

Adolescent↗

Seizure anticipation in human neocortical partial epilepsy.

The transition of brain activity towards an epileptic seizure is still a poorly understood phenomenon. Dynamic changes in brain activity have been detected several minutes before seizure emergence in populations of patients with mesial temporal lobe epilepsy (MTLE), using non-linear analysis of intracranial EEG recordings. Similar detection of a pre-ictal state has been obtained with standard scalp EEG recordings using a modified non-linear method. Here we applied this strategy to the seizures of patients with neocortical partial epilepsy. Results obtained by non-linear similarity analysis of 41 seizures from 11 patients with refractory partial epilepsy originating from various sites of the neocortex showed that (i) a pre-ictal state was detected in 90% of the patients and in 83% of the seizures whatever their location, with a mean anticipation time of 7.5 min; (ii) similar pre-ictal dynamic changes were detected when non-linear analysis methods were applied to either intracranial or scalp EEG recordings; (iii) the recording sites exhibiting these pre-ictal changes were distributed both within the epileptogenic focus and at remote locations; (iv) most pre-ictal dynamic changes were not correlated with linear changes in the frequency spectrum or with changes in the visually inspected EEG and the patients' behaviour. Hypotheses on the neuronal mechanisms underlying the pre-ictal period are discussed. The present results, together with those recently obtained in an MTLE population, suggest that changes in pre-ictal dynamics are a general phenomenon associated with seizure emergence in a wide population of patients with partial epilepsy, wherever the epileptogenic focus is located. The possibility of anticipating the onset of seizures has considerable therapeutic implications.

Adolescent↗

Recent developments in treatment of status epilepticus: a review.

Considering that status epilepticus (SE) is a medical emergency associated with significant morbidity and mortality, there are surprisingly few evidence-based data to guide management decisions. The purpose of this review is to give an overview of the incidence and classification of SE and to summarise the recent developments in the treatment of generalized tonic clonic status epilepticus (GTCSE). These consist in two prospective randomised studies indicating that SE should be treated as soon as possible, even out-of hospital, by intravenous (IV) benzodiazepine. Lorazepam is probably the best choice for the initial therapy. However, the differences in efficacy as compared to diazepam, diazepam associated to phenytoin or phenobarbital were not significant. There is no Class I evidence to help us choose which drug to give in SE that is not responsive to the initial lorazepam. Traditionally, based on a long clinical experience, IV phenytoin is given as the second drug. Recently, phenytoin is being increasingly substituted by fosphenytoin, even though no formal, comparative tolerability studies have been performed to study this compound in GTCSE. Starting in the 1980's, the use of injectable valproic acid (IV VPA) has been reported in an increasing number of uncontrolled case series initiated by doctors, indicating relative easy use, relative good tolerability and suggesting that it may be efficacious. Finally, we have very little data concerning the treatment of SE refractory to a benzodiazepine and phenytoin. Despite this lack of data many centres today use midazolam or propofol rather than phenobarbital or pentobarbital in this setting because these compounds have short half-lives and are, therefore, easier to handle.

Anticonvulsants↗