Jean-Pierre Vignal

Clinical classification of psychogenic non-epileptic seizures based on video-EEG analysis and automatic clustering

Background Psychogenic non-epileptic seizures (PNES) or attacks consist of paroxysmal behavioural changes that resemble an epileptic seizure but are not associated with electrophysiological epileptic changes. They are caused by a psychopathological process and are primarily diagnosed on history and video-EEG. Clinical presentation comprises a wide range of symptoms and signs, which are individually neither totally specific nor sensitive, making positive diagnosis of PNES difficult. Consequently, PNES are often misdiagnosed as epilepsy. The aim of this study was to identify homogeneous groups of PNES based on specific combinations of clinical signs with a view to improving timely diagnosis. Methods The authors first retrospectively analysed 22 clinical signs of 145 PNES recorded by video-EEG in 52 patients and then conducted a multiple correspondence analysis and hierarchical cluster analysis. Results Five clusters of signs were identified and named according to their main clinical features: dystonic attack with primitive gestural activity (31.6%); pauci-kinetic attack with preserved responsiveness (23.4%); pseudosyncope (16.9%); hyperkinetic prolonged attack with hyperventilation and auras (11.7%); axial dystonic prolonged attack (16.4%). When several attacks were recorded in the same patient, they were automatically classified in the same subtype in 61.5% of patients. Conclusion This study proposes an objective clinical classification of PNES based on automatic clustering of clinical signs observed on video-EEG. It also suggests that PNES are stereotyped in the same patient. Application of these findings could help provide an objective diagnosis of patients with PNES.

Intracranial evaluation of the epileptogenic zone in regional infrasylvian polymicrogyria

Purpose:u2002 To define the relationship between the epileptogenic zone and the polymicrogyric area using intracranial electroencephalography (EEG) recordings in patients with structural epilepsy associated with regional infrasylvian polymicrogyria (PMG).

Psychogenic nonepileptic seizures: Characterization of two distinct patient profiles on the basis of trauma history

This prospective study investigated and compared psychiatric features of 25 consecutive patients with psychogenic nonepileptic seizures (PNES) on the basis of presence of reported trauma. The trauma group comprised 19 patients (76%) and the no-trauma group comprised 6 patients (34%). We compared history of PNES, psychiatric comorbidity, alexithymia, and symptoms of dissociation. The study clearly characterized two distinct profiles of patients with PNES on the basis of trauma history. Patients with trauma had at least one psychiatric comorbidity or antecedent (vs 0% in the no-trauma group NT, P<0.001) and a higher median score of dissociation (P<0.001). Patients without trauma had more frequent frustration situations as a factor triggering PNES and subsequent sick leaves as perpetuating factors (P=0.001). Trauma antecedents correlated with a high rate of psychiatric comorbidity and a strong dissociative mechanism. Patients without trauma had no psychiatric comorbidity and a weaker dissociative mechanism.

Electrical source imaging in cortical malformation–related epilepsy: A prospective EEG‐SEEG concordance study

Delineation of the epileptogenic zone (EZ) in refractory epilepsy related to malformations of cortical development (MCDs) often requires intracranial electroencephalography (EEG) recordings, especially in cases of negative magnetic resonance imaging (MRI) or discordant MRI and video‐EEG findings. It is therefore crucial to promote the development of noninvasive methods such as electrical source imaging (ESI). We aimed to (1) analyze the localization concordance of ESI derived from interictal discharges and EZ estimated by stereo‐EEG (SEEG); (2) compare the concordance of ESI, MRI, and electroclinical correlations (ECCs) with SEEG‐EZ; and (3) assess ESI added value in the EZ localization.

Catching the invisible: mesial temporal source contribution to simultaneous EEG and SEEG recordings

Mesial temporal sources are presumed to escape detection in scalp electroencephalographic recordings. This is attributed to the deep localization and infolded geometry of mesial temporal structures that leads to a cancellation of electrical potentials, and to the blurring effect of the superimposed neocortical background activity. In this study, we analyzed simultaneous scalp and intracerebral electroencephalographic recordings to delineate the contribution of mesial temporal sources to scalp electroencephalogram. Interictal intracerebral spike networks were classified in three distinct categories: solely mesial, mesial as well as neocortical, and solely neocortical. The highest and earliest intracerebral spikes generated by the leader source of each network were marked and the corresponding simultaneous intracerebral and scalp electroencephalograms were averaged and then characterized both in terms of amplitude and spatial distribution. In seven drug-resistant epileptic patients, 21 interictal intracerebral networks were identified: nine mesial, five mesial plus neocortical and seven neocortical. Averaged scalp spikes arising respectively from mesial, mesial plus neocortical and neocortical networks had a 7.1 (nxa0=xa01,949), 36.1 (nxa0=xa0628) and 10 (nxa0=xa01,471)xa0µV average amplitude. Their scalp electroencephalogram electrical field presented a negativity in the ipsilateral anterior and basal temporal electrodes in all networks and a significant positivity in the fronto-centro-parietal electrodes solely in the mesial plus neocortical and neocortical networks. Topographic consistency test proved the consistency of these different scalp electroencephalogram maps and hierarchical clustering clearly differentiated them. In our study, we have thus shown for the first time that mesial temporal sources (1) cannot be spontaneously visible (mean signal-to-noise ratio −2.1xa0dB) on the scalp at the single trial level and (2) contribute to scalp electroencephalogram despite their curved geometry and deep localization.

Direct evidence of nonadherence to antiepileptic medication in refractory focal epilepsy

The adherence to medication in drug‐resistant focal epilepsy (RFE) remains largely unknown. The present work aimed to assess the frequency of recent adherence to antiepileptic drugs (AEDs) in patients with RFE. This prospective observational study screened all patients with RFE, admitted to the Nancy University Hospital between April 2006 and September 2008, for a 5‐day hospitalization without AED tapering. The adherence to AEDs was assessed by measuring serum drug levels on day 1 (reflecting the recent “at home” adherence) and day 5 (reflecting the individual reference concentration when drug ingestion was supervised). A patient was considered nonadherent if at least one of their serum drug levels was different between days 1 and 5. The day‐1 value was considered different from day 5 when it was at least 30% lower (underdosed) or 30% higher (overdosed). Nonadherent patients were classified as under‐consumers in the case of one or more underdosed day‐1 values, over‐consumers in the case of one or more overdosed day‐1 values, or undefined if they exhibited both underdosed and overdosed day‐1 values. Forty‐four of the 48 screened patients were included. Eighteen (40.9%) of 44 patients were nonadherent. Among them, 12 (66.7%) were over‐consumers, 4 (22.2%) were under‐consumers, and 2 (11.1%) were undefined nonadherents. The study indicates that recent adherence to antiepileptic medication in this group of patients with RFE is poor. Overconsumption is the most frequent form of nonadherence in this population and should be specifically assessed to prevent its possible consequences in terms of AEDs dose‐dependent adverse events.

Effect of hyperventilation on seizure activation: potentiation by antiepileptic drug tapering

Objective To determine prospectively the efficacy of hyperventilation (HV) to activate epileptic seizures and the contribution of antiepileptic drug tapering. Methods Eighty patients with proven epilepsy and referred for long-term video-EEG monitoring were consecutively enrolled from November 2007 to December 2008. A seizure was considered as ‘activated’ if it occurred during HV or within 5u2005min after completion. The rate of activated seizures (number of seizures/h) was compared with the rate of spontaneous seizure. The authors finally compared the effect of HV before and during antiepileptic drug (AED) tapering. Results The authors analysed 247u2005days of monitoring. Among 52 recorded seizures, 18 were activated by HV. The rate of activated seizure was nine times higher than the rate of control seizures (p=0.001). In the subgroup of patients with no AED tapering, there was no significant activating effect of HV on seizures. In the subgroup undergoing AED tapering, the effect of HV was not significant before (p=0.257) but very significant during AED tapering (p<0.004). Discussion The findings confirm that hyperventilation is efficient to activate epileptic seizures in epileptic patients referred for long-term video-EEG monitoring and that this activating effect is mainly related to the potentiating effect of AED tapering. Repeated HVs combined with AED tapering increase the rate of recorded seizures and the diagnostic yield of daytime video-EEG monitoring.

French guidelines on stereoelectroencephalography (SEEG)

Stereoelectroencephalography (SEEG) was designed and developed in the 1960s in France by J.xa0Talairach and J.xa0Bancaud. It is an invasive method of exploration for drug-resistant focal epilepsies, offering the advantage of a tridimensional and temporally precise study of the epileptic discharge. It allows anatomo-electrical correlations and tailored surgeries. Whereas this method has been used for decades by experts in a limited number of European centers, the last ten years have seen increasing worldwide spread of its use. Moreover in current practice, SEEG is not only a diagnostic tool but also offers a therapeutic option, i.e., thermocoagulation. In order to propose formal guidelines for best clinical practice in SEEG, a working party was formed, composed of experts from every French centre with a large SEEG experience (those performing more than 10 SEEG per year over at least a 5 year period). This group formulated recommendations, which were graded by all participants according to established methodology. The first part of this article summarizes these within the following topics: indications and limits of SEEG; planning and management of SEEG; surgical technique; electrophysiological technical procedures; interpretation of SEEG recordings; and SEEG-guided radio frequency thermocoagulation. In the second part, those different aspects are discussed in more detail by subgroups of experts, based on existing literature and their own experience. The aim of this work is to present a consensual French approach to SEEG, which could be used as a basic document for centers using this method, particularly those who are beginning SEEG practice. These guidelines are supported by the French Clinical Neurophysiology Society and the French chapter of the International League Against Epilepsy.

Localizing value of electrical source imaging: Frontal lobe, malformations of cortical development and negative MRI related epilepsies are the best candidates

Objective We aimed to prospectively assess the anatomical concordance of electric source localizations of interictal discharges with the epileptogenic zone (EZ) estimated by stereo-electroencephalography (SEEG) according to different subgroups: the type of epilepsy, the presence of a structural MRI lesion, the aetiology and the depth of the EZ. Methods In a prospective multicentric observational study, we enrolled 85 consecutive patients undergoing pre-surgical SEEG investigation for focal drug-resistant epilepsy. Electric source imaging (ESI) was performed before SEEG. Source localizations were obtained from dipolar and distributed source methods. Anatomical concordance between ESI and EZ was defined according to 36 predefined sublobar regions. ESI was interpreted blinded to- and subsequently compared with SEEG estimated EZ. Results 74 patients were finally analyzed. 38 patients had temporal and 36 extra-temporal lobe epilepsy. MRI was positive in 52. 41 patients had malformation of cortical development (MCD), 33 had another or an unknown aetiology. EZ was medial in 27, lateral in 13, and medio-lateral in 34. In the overall cohort, ESI completely or partly localized the EZ in 85%: full concordance in 13 cases and partial concordance in 50 cases. The rate of ESI full concordance with EZ was significantly higher in (i) frontal lobe epilepsy (46%; p = 0.05), (ii) cases of negative MRI (36%; p = 0.01) and (iii) MCD (27%; p = 0.03). The rate of ESI full concordance with EZ was not statistically different according to the depth of the EZ. Significance We prospectively demonstrated that ESI more accurately estimated the EZ in subgroups of patients who are often the most difficult cases in epilepsy surgery: frontal lobe epilepsy, negative MRI and the presence of MCD.

sEEG is a Safe Procedure for a Comprehensive Anatomic Exploration of the Insula: A Retrospective Study of 108 Procedures Representing 254 Transopercular Insular Electrodes

BACKGROUNDnThe exploration of the insula in pre-surgical evaluation of epilepsy is considered to be associated with a high vascular risk resulting in an incomplete exploration of the insular cortex.nnnOBJECTIVEnTo report a retrospective observational study of insular exploration using stereoelectroencephalography (sEEG) with transopercular and parasagittal oblique intracerebral electrodes from January 2008 to January 2016. The first purpose of this study was to evaluate the surgical risks of insular cortex sEEG exploration. The second purpose was to define the ability of placing intracerebral contacts in the whole insular cortex.nnnMETHODSnNinety-nine patients underwent 108 magnetic resonance imaging (MRI)-guided stereotactic implantations of intracerebral electrodes in the context of preoperative assessment of drug-resistant epilepsy, including at least 1 electrode placed in the insular cortex. On postoperative computed tomography images co-registered with MRI, followed by MRI segmentation and application of a transformation matrix, intracerebral contact coordinates of the insular electrodes contacts were anatomically localized in the Talairach space. Finally, dispersion and clustering analysis was performed.nnnRESULTSnThere was no morbidity, in particular hemorrhagic complications, or mortality related to insular electrodes. Statistical comparison of intracerebral contact positions demonstrated that whole insula exploration is possible on the left and right sides. In addition, the clustering analysis showed the homogeneous distribution of the electrodes within the insular cortex.nnnCONCLUSIONnIn the presurgical evaluation of drug-resistant epilepsy, the insular cortex can be explored safely and comprehensively using transopercular sEEG electrodes. Parasagittal oblique trajectories may also be associated to achieve an optimal exploration.