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Abstract Wearable seizure detection devices have the potential to address unmet needs of people with epilepsy. A recently published evidence‐based international guideline recommends using such devices for safety indications in patients with tonic–clonic seizures (TCS). Our objective was to map existing guidelines and clinical practices at national level. We conducted a survey of the International League Against Epilepsy (ILAE) chapters regarding national recommendations and practical circumstances for prescribing seizure detection devices, and another survey of physicians in the ILAE constituency anywhere in the world, concerning their views and practices regarding recommendations for and prescription of such devices. Fifty‐eight ILAE chapters (response rate 48%) and 157 physicians completed the surveys. More than two‐thirds of responding countries do not have standards on wearables for seizure detection, although they indicated availability of such devices. The most often recognized indications were safety and objective seizure quantification. In nearly half of countries, devices are purchased by patients or caregivers, and either lack a uniform reimbursement scheme (41%) or patients pay the full cost for the device (48%). Tonic–clonic seizure frequency, nocturnal seizures, and previous injuries were the main factors that influenced the surveyed physicians to recommend wearable seizure detection devices. Our results document the need to implement international clinical practice guidelines at national level and to consider these when deciding upon reimbursement of seizure detection devices.

Abstract The severely ozone‐depleting trichlorofluoromethane is still appearing in several recycling processes or industrial applications. A simple and selective supramolecular complex formation of per‐methylated α‐cyclodextrin (1) with the highly volatile trichlorofluoromethane (2) is reported. This interaction moreover leads to thermally stable crystals. Per‐methylated α‐cyclodextrin is successfully exploited as a reversible and selective adsorption material for liquid and airborne trichlorofluoromethane as well as an affinity material for the chemical sensing and detection of this particular volatile organic component.

Abstract Introduction Sudden unexpected death in patients with epilepsy (SUDEP) remains a poorly understood entity, and it is unclear whether the same pathomechanisms underlie all sudden deaths occurring in patients with epilepsy. One aspect not included in current models of SUDEP is the role of increased intracranial pressure (ICP) which can be observed immediately upon seizure activity in neurosurgical practice. Methods We conducted a systematic review of the occurrence of edema in patients with epilepsy reported to have died of sudden death who underwent brain autopsy or postmortem brain imaging and discuss how increased ICP may contribute to clinical features of SUDEP. Results 19 eligible studies comprising a total of 623 patients were identified. Edema—mostly mild or moderate—was reported in 17% of cases and 74% of studies. 1% (n = 6) of the overall cases were clearly identified as having Dravet syndrome or an SCN1A mutation. In these patients, edema was found in 4 (67%) of cases. Conclusion Edema is regularly found in patients with epilepsy classified to have died from SUDEP. We argue that seizures preceding SUDEP may in certain cases elicit acute edema which may represent an additional contributing factor in the cascade of events leading to sudden death of patients with epilepsy. Furthermore, we hypothesize that mild edema may especially progress to severe edema in patients with sodium channel mutations which may represent an important mechanism to investigate in the context of understanding the significantly elevated risk of SUDEP in patients with SCN1A mutations.

Epilepsy surgery is the therapy of choice for many patients with drug-resistant focal epilepsy. Recognizing and describing ictal and interictal patterns with intracranial electroencephalography (EEG) recordings is important in order to most efficiently leverage advantages of this technique to accurately delineate the seizure-onset zone before undergoing surgery. In this seminar in epileptology, we address learning objective "1.4.11 Recognize and describe ictal and interictal patterns with intracranial recordings" of the International League against Epilepsy curriculum for epileptologists. We will review principal considerations of the implantation planning, summarize the literature for the most relevant ictal and interictal EEG patterns within and beyond the Berger frequency spectrum, review invasive stimulation for seizure and functional mapping, discuss caveats in the interpretation of intracranial EEG findings, provide an overview on special considerations in children and in subdural grids/strips, and review available quantitative/signal analysis approaches. To be as practically oriented as possible, we will provide a mini atlas of the most frequent EEG patterns, highlight pearls for its not infrequently challenging interpretation, and conclude with two illustrative case examples. This article shall serve as a useful learning resource for trainees in clinical neurophysiology/epileptology by providing a basic understanding on the concepts of invasive intracranial EEG., (© 2024 The Authors. Epileptic Disorders published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background and Purpose: A clinical risk score for sudden unexpected death in epilepsy (SUDEP) in patients with drug-resistant focal epilepsy could help improve prevention., Methods: A case-control study was conducted including (i) definite or probable SUDEP cases collected by the French National Sentinel Mortality Epilepsy Network and (ii) control patients from the French national research database of epilepsy monitoring units. Patients with drug-resistant focal epilepsy were eligible. Multiple logistic regressions were performed. After sensitivity analysis and internal validation, a simplified risk score was developed from the selected variables., Results: Sixty-two SUDEP cases and 620 controls were included. Of 21 potential predictors explored, seven were ultimately selected, including generalized seizure frequency (>1/month vs. <1/year: adjusted odds ratio [AOR] 2.6, 95% confidence interval [CI] 1.25-5.41), nocturnal or sleep-related seizures (AOR 4.49, 95% CI 2.68-7.53), current or past depression (AOR 2.0, 95% CI 1.19-3.34) or the ability to alert someone of an oncoming seizure (AOR 0.57, 95% CI 0.33-0.98). After internal validation, a clinically usable score ranging from -1 to 8 was developed, with high discrimination capabilities (area under the receiver operating curve 0.85, 95% CI 0.80-0.90). The threshold of 3 has good sensitivity (82.3%, 95% CI 72.7-91.8), whilst keeping a good specificity (82.7%, 95% CI 79.8-85.7)., Conclusions: These results outline the importance of generalized and nocturnal seizures on the occurrence of SUDEP, and show a protective role in the ability to alert someone of an oncoming seizure. The SUDEP-CARE score is promising and will need external validation. Further work, including paraclinical explorations, could improve this risk score., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Focal seizures originating from the temporal lobe are commonly associated with peri-ictal hypoxemia (PIH). During the course of temporal lobe seizures, epileptic discharges often not only spread within various parts of the temporal lobe but also possibly insula and frontal lobe. The link between spatial propagation of the seizure discharges and PIH is still unclear. The present study investigates the involvement of several brain structures including medial temporal structures, temporal pole, anterior insula, and frontal cortex in the occurrence of PIH. Using quantitative indices obtained during SEEG (stereoencephalography) recordings in 38 patients, we evaluated the epileptogenicity, the spatial propagation, and functional connectivity between those structures during seizures leading to PIH. Multivariate statistical analyses of SEEG quantitative indices showed that temporal lobe seizures leading to PIH are characterized by a strong involvement of amygdala and anterior insula during seizure propagation and a more widespread involvement of medial temporal lobe structures, lateral temporal lobe, temporal pole, and anterior cingulate at the end of the seizures. On the contrary, seizure-onset zone was not associated with PIH occurrence. During seizure propagation, anterior insula, temporal pole, and temporal lateral neocortex activities were correlated with intensity of PIH. Lastly, PIH occurrence was also related to a widespread increase of synchrony between those structures. Those results suggest that PIH occurrence during temporal lobe seizures may be related to the activation of a widespread network of cortical structures, among which amygdala and anterior insula are key nodes., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

This educational topical review and Task Force report aims to address learning objectives of the International League Against Epilepsy (ILAE) curriculum. We sought to extract detailed features involving semiology from video recordings and interpret semiological signs and symptoms that reflect the likely localization for focal seizures in patients with epilepsy. This glossary was developed by a working group of the ILAE Commission on Diagnostic Methods incorporating the EEG Task Force. This paper identifies commonly used terms to describe seizure semiology, provides definitions, signs and symptoms, and summarizes their clinical value in localizing and lateralizing focal seizures based on consensus in the published literature. Video-EEG examples are included to illustrate important features of semiology in patients with epilepsy.

People with epilepsy have a three-fold increased risk of dying prematurely, and a significant proportion is due to sudden cardiac death or acute myocardial infarctions. The causes of increased cardiovascular morbidity and mortality in epilepsy are manifold and include acute or remote effects of epileptic seizures, the longstanding epilepsy itself or antiseizure treatments. Seizure-related cardiac arrhythmias are common and comprise bradyarrhythmia and asystole, atrial fibrillation and ventricular tachycardia. The most frequent clinically relevant seizure-related arrhythmia is ictal asystole that may require implantation of a cardiac pacemaker, whereas seizure-related ventricular tachycardias are only rarely reported. Takotsubo cardiomyopathy and myocardial infarction are rare complications and predominantly described in association with tonic-clonic seizures. Epilepsy-related cardiac complications include a disturbed cardiac autonomic nervous system and acquired dysfunction of the heart (recently defined as 'epileptic heart'), probably contributing to the abnormalities of cardiac repolarisation and elevated risk of sudden cardiac death in people with epilepsy. If successful, the use of antiseizure medication prevents seizure-related cardiac arrhythmias and remote cardiac complications. However, enzyme-inducing antiseizure medications have a negative impact on cardiovascular risk factors, which may further be aggravated by weight gain linked to specific antiseizure drugs. Given the severe consequences of cardiac risks, the aim of this educational review is to explain the many facets of cardiac complications and their underlying causes, and to enable the reader to recognize and manage these risks with the goal to mitigate the cardiac risks in people with epilepsy. Features of syncope are explained in detail, as syncope of all origins can be mistaken as epileptic seizures in people with or without epilepsy, and ictal syncope (i.e. seizure-induced syncope) can easily be ignored.

Background and Purpose: Some epilepsy syndromes (sleep-related epilepsies, SREs) have a strong link with sleep. Comorbid sleep disorders are common in patients with SRE and can exert a negative impact on seizure control and quality of life. Our purpose was to define the standard procedures for the diagnostic pathway of patients with possible SRE (scenario 1) and the general management of patients with SRE and comorbidity with sleep disorders (scenario 2)., Methods: The project was conducted under the auspices of the European Academy of Neurology, the European Sleep Research Society and the International League Against Epilepsy Europe. The framework entailed the following phases: conception of the clinical scenarios; literature review; statements regarding the standard procedures. For the literature search a stepwise approach starting from systematic reviews to primary studies was applied. Published studies were identified from the National Library of Medicine's MEDLINE database and Cochrane Library., Results: Scenario 1: Despite a low quality of evidence, recommendations on anamnestic evaluation and tools for capturing the event at home or in the laboratory are provided for specific SREs. Scenario 2: Early diagnosis and treatment of sleep disorders (especially respiratory disorders) in patients with SRE are likely to be beneficial for seizure control., Conclusions: Definitive procedures for evaluating patients with SRE are lacking. Advice is provided that could be of help for standardizing and improving the diagnostic approach of specific SREs. The importance of identifying and treating specific sleep disorders for the management and outcome of patients with SRE is underlined., (© 2020 European Academy of Neurology and European Sleep Research Society.)

Background: Paired-pulse (PP) paradigms are commonly employed to assess in vivo cortical excitability using transcranial magnetic stimulation (TMS) to stimulate the primary motor cortex and modulate the induced motor evoked potential (MEP). Single-pulse cortical direct electrical stimulation (DES) during intracerebral EEG monitoring allows the investigation of brain connectivity by eliciting cortico-cortical evoked potentials (CCEPs). However, PP paradigm using intracerebral DES has rarely been reported and has never been previously compared with TMS., Objective: The work was intended (i) to verify that the well-established modulations of MEPs following PP TMS remain similar using DES in the motor cortex, and (ii) to evaluate if a similar pattern could be observed in distant cortico-cortical connections through modulations of CCEP., Methods: Three patients undergoing intracerebral EEG monitoring with electrodes implanted in the central region were studied. Single-pulse DES (1-3 mA, 1 ms, 0.2 Hz) and PP DES using six interstimulus intervals (5, 15, 30, 50, 100, and 200 ms) in the motor cortex with concomitant recording of CCEPs and MEPs in contralateral muscles were performed. Finally, a navigated PP TMS session targeted the intracranial stimulation site to record TMS-induced MEPs in two patients., Results: MEP modulations elicited by PP intracerebral DES proved similar among the three patients and to those obtained by PP TMS. CCEP modulations elicited by PP intracerebral DES usually showed a pattern comparable to that of MEP, although a different pattern could be observed occasionally., Conclusion: PP intracerebral DES seems to involve excitatory and inhibitory mechanisms similar to PP TMS and allows the recording of intracortical inhibition and facilitation modulation on cortico-cortical connections. Hum Brain Mapp 37:3767-3778, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Ictal anxiety is a frequent epileptic symptom; it is usually brief, associated with objective clinical signs, and is not positively influenced by external factors, in contrast to psychiatric disorders. These criteria can, however, be misleading, especially in patients with psychiatric comorbidities. We report two patients with a history of drug-resistant right temporal lobe epilepsy, who developed long-lasting psychiatric symptoms, suggestive of exacerbation of their comorbid anxiety disorder. However, intracranial EEG data and [(18)F] FDG-PET suggested that these symptoms were related to seizure activity, highlighting the difficulties in differentiating ictal symptoms from psychiatric episodes in some patients with epilepsy and comorbid psychiatric disorders. [Published with video sequence].

Aim: A high rate of abnormal social behavioural traits or perceptual deficits is observed in children with unilateral temporal lobe epilepsy. In the present study, perception of auditory and visual social signals, carried by faces and voices, was evaluated in children or adolescents with temporal lobe epilepsy., Methods: We prospectively investigated a sample of 62 children with focal non-idiopathic epilepsy early in the course of the disorder. The present analysis included 39 children with a confirmed diagnosis of temporal lobe epilepsy. Control participants (72), distributed across 10 age groups, served as a control group. Our socio-perceptual evaluation protocol comprised three socio-visual tasks (face identity, facial emotion and gaze direction recognition), two socio-auditory tasks (voice identity and emotional prosody recognition), and three control tasks (lip reading, geometrical pattern and linguistic intonation recognition). All 39 patients also benefited from a neuropsychological examination., Results: As a group, children with temporal lobe epilepsy performed at a significantly lower level compared to the control group with regards to recognition of facial identity, direction of eye gaze, and emotional facial expressions. We found no relationship between the type of visual deficit and age at first seizure, duration of epilepsy, or the epilepsy-affected cerebral hemisphere. Deficits in socio-perceptual tasks could be found independently of the presence of deficits in visual or auditory episodic memory, visual non-facial pattern processing (control tasks), or speech perception. A normal FSIQ did not exempt some of the patients from an underlying deficit in some of the socio-perceptual tasks., Conclusion: Temporal lobe epilepsy not only impairs development of emotion recognition, but can also impair development of perception of other socio-perceptual signals in children with or without intellectual deficiency. Prospective studies need to be designed to evaluate the results of appropriate re-education programs in children presenting with deficits in social cue processing.

Objectives: The aim of our study was to explore the functional connectivity between the insula and other cortical regions, in human, using cortico-cortical evoked potentials (CCEPs), Experimental Design: We performed intra-cerebral electrical stimulation in eleven patients with refractory epilepsy investigated with depth electrodes, including 39 targeting the insula. Electrical stimulation consisted of two series of 20 pulses of 1-ms duration, 0.2-Hz frequency, and 1-mA intensity delivered at each of the 39 insular bipoles. Rates of connectivity were reported whenever a noninsular cortical region was tested by at least ten stimulating/recording electrode pairs in three or more patients, Results: Significant CCEPs were elicited in 193 of the 578 (33%) tested connections, with an average latency of 33 ± 5 ms. The highest connectivity rates were observed with the nearby perisylvian structures (59%), followed by the pericentral cortex (38%), the temporal neocortex (28%), the lateral parietal cortex (26%), the orbitofrontal cortex (25%), the mesial temporal structures (24%), the dorsolateral frontal cortex (15%), the temporal pole (14%), and the mesial parietal cortex (11%). No connectivity was detected in the mesial frontal cortex or cingulate gyrus. The pattern of connectivity also differed between the five insular gyri, with greater connectivity rate for the posterior short gyrus (49%), than for the middle short (29%), and two long gyri (28 and 33%), Conclusion: The human insula is characterized by a rich and complex connectivity that varies as a function of the insular gyrus and appears to partly differ from the efferences described in nonhuman primates., (Copyright © 2014 Wiley Periodicals, Inc.)

Objectives: The anatomical organization of the insular cortex is characterized by its rich and heterogeneous cytoarchitecture and its wide network of connections. However, only limited knowledge is available regarding the intrainsular connections subserving the complex integrative role of the insular cortex. The aim of this study was to analyze the functional connectivity within- and across-insular subregions, at both gyral and functional levels., Experimental Design: We performed intracerebral electrical stimulation in 10 patients with refractory epilepsy investigated with depth electrodes, 38 of which were inserted in the insula. Bipolar electrical stimulation, consisting of two series of 20 pulses of 1-ms duration, 0.2-Hz frequency, and 1-mA intensity, was delivered at each insular contact. For each stimulated insular anatomical region, we calculated a rate of connectivity, reflecting the proportion of other insular contacts, showing significant evoked potentials., Results: Statistically significant evoked potentials were recorded in 74% of tested connections, with an average latency of 26 ± 3 ms. All insular gyri were interconnected, except the anterior and posterior short gyri. Most connections were reciprocal, showing no clear anterior to posterior directionality. No connection was observed between the right and the left insula., Conclusions: These findings point to specific features of human insula connectivity as compared to non-Human primates, and remain consistent with the complex integration role devoted to the human insula in many cognitive domains. Periodicals, Inc., (Copyright © 2013 Wiley Periodicals, Inc.)

The greater reliability of randomised controlled trials (RCTs) over non-randomised studies to objectively assess efficacy and/or safety of new therapeutic interventions is one of the main paradigms which sustains the evidence-based decision process in clinical practice. This assumption is primarily based on the hypothesis that randomisation, and particularly blinding procedure, drastically reduces the potential bias related to the preferences of patients and physicians. However, from non-randomised studies to double-blind, placebo-controlled RCTs, the preferences of patients and physicians can impact the evaluation of treatment effectiveness. Both internal validity and external validity of RCTs are impacted by various biases related to patient and physician preferences. Thus, influence of patient and physician expectations on trial outcomes might be much less trivial than expected, both in open-label and double-blind, placebo-controlled, randomised trials. Accordingly, it might be interesting to systematically collect information about patient preferences before randomisation, using dedicated questionnaires, in order to be able to evaluate the impact of non-preferred allocation on trial results.

Evaluating the outcome of our own actions is a fundamental process by which we adapt our behavior in our interaction with the external world. fMRI and electrophysiological studies in monkeys have found feedback-specific responses in several brain regions, unveiling facets of a large-scale network predominantly distributed in the frontal lobes. However, a consensus has yet to be reached regarding the exact contribution of each region. The present study benefited from intracerebral EEG recordings in epileptic patients to record directly the neural activity in each of those frontal structures in response to positive and negative feedback. Both types of feedback induced a sequence of high-frequency responses (>40 Hz) in a widespread network involving medial frontal cortex, dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), and insular cortex. The pre-supplementary motor area (pre-SMA), DLPFC, and lateral OFC showed higher activation in response to negative feedback, while medial OFC and dorsal anterior cingulate cortex (dACC) were more responsive to positive feedback. Responses in the medial prefrontal cortex (pre-SMA and dACC) were sustained (lasting more than 1,000 ms), while responses in the DLPFC, insula, and the OFC were short lasting (less than 800 ms). Taken together, our findings show that evaluating the outcome of our actions triggers gamma-range activity modulations in several frontal and insular regions. Moreover, we found that the timing and amplitude of those gamma-band responses reveal fine-scale dissociations between the neural dynamics of positive versus negative feedback processing., (2010 Wiley-Liss, Inc.)

Mutations in the eukaryotic translation initiation factor 2B (eIF2B) represent a heterogenous group of autosomal recessive leucodystrophy characterized by a diffuse CSF-like aspect of the white matter at MRI designed as vanishing white matter (VWM) and episodes of acute deterioration after stresses. The mild juvenile and adult forms are often associated with primary ovarian failure, a syndrome referred to as ovarioleukodystrophy (OLD). We reported case of a woman with OLD who successfully underwent in vitro fertilization with donated oocytes and embryo transfer. Pregnancy was complicated by a non-convulsive epileptic status leading to the identification of compound heterozygous EIF2B5 mutation (p.Arg113His and p.Arg299His). The patient gave birth to a healthy child by Caesarean section. In conclusion, we report for the first time that in vitro fertilization and embryo transfer can lead to a successful procreation in patients with OLD related to EIF2B mutations. However this procedure must be considered with cautiousness, because of its potential neurological risks.

Recent data have demonstrated that insular seizures can mimic those encountered in temporal lobe epilepsy (TLE), as well as nocturnal hypermotor attacks suggestive of nocturnal frontal lobe epilepsy (NFLE). To illustrate some of the issues raised by these observations, we report our first two patients with suspected TLE and NFLE, respectively, in whom we originally demonstrated an insular ictal onset zone. Patient 1 suffered from daytime seizures characterised by a rising and distressing epigastric sensation rapidly followed by oro-alimentary automatisms, associated with right temporal scalp-EEG ictal discharge. Neuroimaging showed consistent right temporal abnormalities, including MRI signs of hippocampal sclerosis, anterior and mesial glucose hypometabolism, and mesial decrease of benzodiazepine receptors. Intra-cerebral EEG investigation was primarily performed because of several ictal signs and symptoms suggesting a rapid involvement of the perisylvian region, and showed that the patient suffered two types of seizure, one of which arose from the mesial temporal structures, the other was sleep-related and originated in the posterior-inferior portion of the insula. Anterior temporal lobectomy failed to control this second type of seizure. Patient 2 suffered from brief, nocturnal, hypermotor seizures characterised by an indefinable aura followed by agitation, body rolling, scream and pelvic thrust. Interictal and ictal scalp-EEG failed to detect epileptiform discharges, whereas neuroimaging showed left mesial frontal, glucose hypometabolism and decreased benzodiazepine receptors associated with a left fronto-basal arachnoidal cyst. Invasive EEG monitoring was performed with the aim of identifying an orbital or mesial frontal ictal onset, but eventually demonstrated that the seizure originated in the anterior-superior portion of the left insula. The patient did not undergo surgery and died of SUDEP two years later. We discuss the heterogeneity of insular seizure semiology according to functional anatomy, the clinical signs and symptoms that might suggest an insular ictal onset, the indications and types of invasive EEG monitoring that are needed to identify an insular epileptogenic zone definitively, as well as potential surgical treatment.

The definition of the epileptogenic zone, as proposed by Talairach and Bancaud, is an ictal electro-clinical definition based on the results of stereotactic intracerebral EEG (SEEG) recordings. It takes into account not only the anatomical location of the "site of the beginning and of the primary organization" of the epileptic discharge, but also how this discharge gives rise to the accompanying clinical symptoms. This definition is different from the North American view since, for the French authors, the epileptogenic zone is not synonymous with what can be called the "what-to-remove area". In fact, it is above all a conceptual definition which emphazises the importance of studying the spatio-temporal dynamics of seizure discharges, and not only their starting point.

Presurgical evaluation for patients with drug-resistant epilepsy requires the definition of various zones that have a variable spatial relationship with the epileptogenic zone. All the available methods to directly measure the actual seizure-onset zone and to define "the minimum amount of cortical tissue that must be resected to produce seizure-freedom" have significant limitations. We report on the case of a patient with dual pathology (hippocampal sclerosis and a post-traumatic scar) and discuss the contribution of the various presurgical investigations that led to surgery and seizure-freedom.

Patients with refractory epilepsy suffer from an increased risk of death, primarily due to seizure-related fatalities including sudden unexpected death (SUDEP), which could be conceivably avoided by surgical cure of the epilepsy. Several series have addressed this issue by comparing the mortality rate between medically and surgically treated drug resistant populations, as well as between patients, seizure free and non seizure free post-operatively. Results from some studies suggest that successful temporal lobe surgery reduced the risk of death to that observed in the normal population, whereas patients who continue to suffer recurrent seizures still present an increased standardized mortality ratio (SMR). However, other series have failed to replicate this finding, or found no difference in the overall mortality and SUDEP rates between operated and medically treated patients. All the above studies suffer various types of methodological limitations, hampering any definite conclusion regarding the impact of epilepsy surgery on mortality. However, part of the apparently discordant reported findings might be reconciled through the following framework. Patients who will eventually respond favourably or unfavourably to an anterior temporal lobectomy might already differ in the risk of seizure-related death, pre-operatively. Specifically, patients whose temporal lobe epileptogenic network extends to the perisylvian region (temporal plus epilepsy) appear to be at higher risk of failed TLE surgery, secondary generalised tonic-clonic seizures, ictal apnoea or insula-driven severe cardiac arrhytmias. This population might carry most of the SUDEP burden, both pre- and post-operatively, accounting for the lack of an obvious net reduction of seizure related deaths after temporal lobe surgery. A multicentric study has recently been launched in order to test this hypothesis, and will hopefully help to conclude on the impact of epilepsy surgery on mortality outcome.

The early prediction of intractability is a major challenge in epileptology. Some prognostic factors have been pointed out, most of which simply underlined that partial epilepsy is more difficult to control than idiopathic generalized epilepsy (IGE). Indeed, the main predictors are the presence of a brain lesion demonstrated by neuroimaging or suggested by a neurological deficit or a developmental delay, as well as electroclinical evidence of non idiopathic partial epilepsy. Little is known about the relationship between the location of the epileptogenic area and the chance of being seizure-free in patients with partial epilepsy. Some data suggest that temporal lobe epilepsy (TLE) is more difficult to control than other partial epilepsies, but this might only reflect the prognostic impact of hippocampal sclerosis. Indeed, several studies have shown that the majority of patients with MRI evidence of hippocampal sclerosis develop refractory epilepsy. This observation also applies to patients with malformation of cortical development (MCD). The response to the first AED is another early predictor of refractory epilepsy. At the time of diagnosis, several prognostic factors are available to predict drug resistance, but further studies are still needed to better delineate the specific role of each of these factors, and to offer a more accurate prediction of long term seizure outcome.

Prosody is an important feature of language and refers to variations in the acoustic properties of timing, intensity and fundamental frequency that are used to convey affective or linguistic information. The prosodic component of ictal speech has not yet been specifically studied in epileptic patients. We report the case of a patient with right mesial temporal lobe epilepsy who developed ictal, recurrent speech utterances associated with an altered prosody during both spontaneous seizures and a very localized stimulation-induced discharge of the non-dominant precentral operculum, a finding consistent with results of functional magnetic resonance imaging studies in healthy subjects. This should prompt future studies, with the aim of better evaluating the localizing value of ictal dysprosody in patients with drug resistant, partial epilepsy.

The localizing and lateralizing values of eye and head ictal deviations during frontal lobe seizures are still matters of debate. In particular, no specific data regarding the origin of ipsilateral head turning in frontal lobe seizures are available. We report a patient with frontal lobe seizures associated with reproducible, early, ipsilateral head deviation, where imaging and video-stereo-electroencephalography data, as well as surgical outcome, demonstrated the fronto-polar and orbito-frontal origin of the epileptic discharge. We conclude that early ipsilateral head deviation, in the context of frontal lobe epilepsy, raises the possibility of fronto-polar or orbito-frontal seizure onset.[Published with video sequences].

The choice of an antiepileptic drug (AED) in patients with epilepsy is mainly based on efficacy and safety of each drug. However, these criteria of drug selection should be further evaluated according to the epileptic syndromes, and adjusted to the sex and age of the patient. Unfortunately, very few studies have been conducted based on these latter criteria. We conducted a survey on the management of epilepsy treatment in adults. This survey was undertaken in France, and led to the establishment of a French consensus on antiepileptic drug treatment in adult patients with newly diagnosed epilepsy. Patients were grouped into 18 categories according to the epileptic syndrome (absence epilepsy, juvenile myoclonic epilepsy, undetermined idiopathic generalized epilepsy, symptomatic or cryptogenic partial epilepsy and unclassified epilepsy), and to the patient's gender and age. Our survey suggests that there is a consensus among French epileptologists for the choice of AEDs, mainly based on the epilepsy syndrome. Gender also plays a crucial role. Sodium valproate and lamotrigine are the two drugs of choice for generalized epilepsies, as well as for undetermined epilepsies. Lamotrigine is often prefered for women of childbearing age. First line AEDs in partial epilepsy are carbamazepine (particularly for men), lamotrigine (particularly for women), and gabapentin (in the elderly). In cases of failure and/or intolerance to one of these AED, the principal alternatives are oxcarbazepine, sodium valproate and topiramate.

In the presurgical assessment of drug refractory partial epilepsies PET represents a privileged means for investigating glucose metabolism and neurotransmission in the functional-deficit zone, defined as the region of cortex that is functioning abnormally in the interictal period. Another aim of PET investigation is to produce images of neurotransmission abnormalities underlying neuronal hyperexcitability, and thus to allow direct visualization of the epileptogenic zone. This approach has been mostly based on the binding of various radio-ligands on specific receptors (GABA-A, opiate and serotonin receptor) and on brain uptake of serotonin precursors. These attempts have not yet been fully validated, in spite of promising studies of serotonin synthesis and receptors. Consequently, at the present state of their development, most of the PET techniques routinely used, reflect changes that are not directly related to the epileptogenic process itself. The lack of large multicentric controlled studies, evaluating the impact of PET, represents the main limitation to a better understanding of the clinical role and utility of PET in epilepsy. We review the basic aspects and limitations of the technique, the various radiopharmaceuticals that have been tested in epilepsy, the sensitivity of the different types of PET investigations, the pathophysiology of PET abnormalities and discuss the practical utility of PET imaging in presurgical assessment of partial epilepsies.

Whether the intrinsic epileptogenicity of hypothalamic hamartomas (HH) is responsible for the entire clinical spectrum of epileptic, neuropsychological and behavioural disorders associated with HH, remains an open issue, in as much as morphologically similar HH can be associated with dramatically different seizure types and cognitive outcomes. The aim of this study was to investigate brain glucose metabolism in patients with epileptogenic HH, in an attempt to identify signs of focal cortical and subcortical dysfunction which might correlate with other clinical data. We have studied five patients with epileptogenic HH using [18F]-fluoro-desoxyglucose and positron emission tomography (FDG-PET). All our patients also underwent an optimal MRI and a video-EEG monitoring, as well as an intra-cranial EEG recording in one of them. The anatomical distribution of FDG-PET abnormalities was compared to that of interictal and ictal electroclinical findings. All five patients demonstrated focal hypometabolism, ipsilateral to the predominant EEG abnormalities and side of HH. Hypometabolic areas greatly varied between patients, but were grossly concordant with the cortical regions suspected to participate in the ictal discharges in each individual. Epileptogenic hypothalamic hamartomas are usually associated with focal cortical hypometabolism in regions which might participate in the overall HH-driven epileptic network. Whether these cortical abnormalities only reflect the propagation of ictal discharges, or a potentially independent seizure onset zone remains unknown.

Patients having a hypothalamic hamartoma (HH) frequently present gelastic or dacrystic seizures, and they often later experience multiple additional seizure types which lead to a severe epileptic encephalopathy. There is now increasing evidence that the HH itself plays a crucial role in this syndrome, but the relationships between the lesion and the different types of seizures remain a questionable issue. Stereotactic intracerebral EEG recordings were performed in 5 patients suffering from a medically intractable epilepsy associated with a HH. The hamartoma was investigated in all cases, and various cortical areas were also evaluated in 4 of the 5 patients. The epileptic discharges arose and remained confined within the hamartoma in 3 of the 4 patients in whom laughing and crying episodes were recorded. In addition, interictal spikes were recorded from the hamartoma in 4 of the 5 patients, whereas the stimulation of the HH could reproduce gelastic or dacrystic episodes in 3. The three patients in whom other types of seizure were recorded showed that the latter were associated with cortical ictal discharges not affecting the HH. Ictal onset appeared either bifrontal, right fronto-central and lateral temporal, or bifrontal with a right side predominance. The cingulate gyrus was involved in all these 3 cases, and the lateralization of the ictal discharges was always ipsilateral to the predominating side of the hamartoma. Interestingly, these seizure types were sometimes immediately preceded by the laughing or crying attacks, as if ictal discharges within the hamartoma triggered those which seemed to originate in the cortex. Therefore, if these findings confirm the intrinsic epileptogenicity of HH, they also demonstrate that epileptic seizures associated with HH can exhibit different types of electroclinical patterns. We propose a speculative pathophysiology in which the mamillo-thalamo-cingulate tract would serve as a relay of HH discharges towards the cortex, the excitability of which would then progressively increase, first leading to cortical interictal epileptiform abnormalities and then to seizures of cortical origin. Whether this proposal of secondary epileptogenesis is valid or not remains a major issue, since it could provide arguments on the moment to discuss surgery.

We report the results of 105 intracortical electrical stimulations of the temporo-polar cortex performed in 30 patients during stereo-electroencephalography (SEEG) investigation of drug-resistant temporal lobe epilepsy. Clinical responses were elicited in 50% of the patients during 26 of the 105 stimulations. Responses are coherent with data found in the literature with mostly psychic, viscero-sensitive, autonomic and viscero-motor phenomena being elicited. Nearly all responses were evoked by stimulation of the antero-medial part of the temporo-polar cortex whereas only once was a clinical response elicited during stimulation of the lateral part of the temporo-polar cortex. Induced auras were more frequently reported when there was an afterdischarge associated to the clinical response (60 and 75% of the stimulation followed by a localized or a diffusing after-discharge, respectively) then when there wasn't any after-discharge following stimulation. The clinical responses evoked during stimulation of the temporo-polar cortex only have a limited topographic specificity since they closely resemble symptoms elicited by stimulation of other limbic or paralimbic areas. Nonetheless these results do suggest that the antero-medial part of the temporo-polar cortex is included in the symptomatogenic zone in so-called "temporo-limbic" epilepsies.

Magnetic resonance imaging (MRI) demonstrates an abnormal aspect of the temporo-polar region in 1/3 to 2/3 of patients suffering from cryptogenic temporal lobe epilepsy. This abnormal aspect is described as a white matter increased T2 signal, resulting in a loss of gray-white matter demarcation, often associated with atrophy, as recently confirmed by quantitative volumetric measurements. These temporo-polar MRI findings appear to correctly lateralize the epileptogenic temporal lobe with a very high specificity, and have never been reported in extra-temporal lobe epilepsy nor in control subjects. They are usually associated with MRI signs of hippocampal sclerosis, but the two conditions seem to be partly distinct from a pathophysiological point of view. Pathological correlates of temporo-polar white matter increased T2 signal are controversial, but the role of an abnormal myelin seems more likely than that of ectopic neurons. A myelin dysfunction would also be consistent with the correlation observed between lateral temporal hypometabolism and temporo-polar MRI abnormalities. Whether or not these MRI findings are associated with a better seizure outcome following temporal lobectomy remains a debated issue.