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Temporal pole epilepsy (TPE) is a poorly known and difficult to individualize subtype of temporal lobe epilepsy. Consequently, in drug-resistant TPE, there is still a debate on the need for a large surgical removal of the temporal pole and mesial temporal structures or a limited resection of the temporal pole. We reviewed all patients who underwent presurgical evaluation for drug-resistant epilepsy over a 17-year period, and report here 19 patients with proven drug-resistant temporal pole epilepsy who underwent a selective temporal pole resection with respect to mesial structures. Most (15) TPE patients exhibited seizures resembling mesiotemporal seizures, whereas the others exhibited nocturnal hyperkinetic seizures or an association of both seizure types. MRI revealed a temporal pole lesion in 58% of patients. Long-term postoperative outcome after a conservative surgery was excellent: 63% of patients were seizure-free (International League Against Epilepsy [ILAE] 1) at 1-year postsurgery and 78% at 5 years. These results show that TPE has no specific electroclinical features but is a distinct type of temporal lobe epilepsy allowing a conservative surgery. Respecting the mesiotemporal structures is a valid surgical approach for drug-resistant temporal pole epilepsy.

5,10-Methylene-tetrahydrofolate reductase (MTHFR) deficiency is a genetic disorder that can occur at any age and can be easily detected by increased homocysteinemia. In adolescence/adult onset forms, the clinical picture is often complex with association of various neurological features and thrombosis. Here we report the cases of two adult siblings who experienced focal epilepsy at 18 years old as a first disease manifestation, without other symptom during several years. Upon diagnosis, both patients received metabolic treatment comprising B9, B12 and betaine which has stopped the occurrence of seizures, allowing discontinuation of anti-epileptic drugs. Among 24 reviewed adolescent/adult onset patients with MTHFR deficiency in the literature, clinical manifestations included gait disorder (96%, from motor central or peripheral origin), cognitive decline (74%), epileptic syndromes (50%), encephalopathy (30%), psychotic symptoms (17%), and thrombotic events (21%). A total of 41% presented a single neurological manifestation that could stay isolated during at least 3 years, delaying achievement of the diagnosis. Brain MRI showed a mostly periventricular white matter changes in 71% of cases. All patients stabilized or improved following metabolic treatment. Despite being rare, adolescence/adult onset MTHFR deficiency can nevertheless be successfully treated. Therefore, homocysteinemia should be tested in various unexplained neuro-psychiatric syndromes like epilepsy or spastic paraparesis, even if isolated, since waiting for completion of the clinical picture is likely to increase the risk of irreversible neurological damage. Electronic supplementary material The online version of this article (10.1186/s13023-018-0767-9) contains supplementary material, which is available to authorized users.

International audience; Epileptic syndromes are distinctive disorders with specific features, which when taken together, permit a specific diagnosis. There is actually a debate on that medial temporal lobe epilepsy with hippocampal sclerosis is an epileptic syndrome. To address this issue, we searched for discriminative semiological features between temporal lobe epilepsy patients with hippocampal sclerosis (TLE-HS patients or group 1), TLE patients with medial structural lesion other than hippocampal sclerosis or in MRI-negative cases with medial onset on further investigations (group 2) and lateral TLE patients (LTLE or group 3). We retrospectively collected data from medical and EEG-video records of 523 TLE patients, referred for surgery to the Pitié-Salpêtrière Epileptology Unit between 1991 and 2014. We identified 389 patients belonging to group 1, 61 patients belonging to group 2, and 73 patients belonging to group 3 and performed a comparative analysis of their clinical data and surgical outcomes. TLE-HS patients (group 1): (1) began epilepsy earlier (11 ± 9 vs. 20 ± 10 vs. 15 ± 9 years); (2) exhibited more frequently early febrile convulsions (FC) (59 vs 7 vs 5%); (3) presented more: ictal gestural automatisms (90 vs 54 vs 67%), dystonic posturing (47 vs 20 vs 23%), and secondary generalized tonic–clonic seizures (GTCS) (70 vs 44% vs 48%) as compared to both groups 2 and 3 patients (all p < 0.001). With respect to auras, abdominal visceral auras were more reported by TLE-HS than by LTLE patients (49 vs 16%). Three cardinal criteria correctly classified 94% of patients into TLE-HS group: history of FC, dystonic posturing, and secondary GTCS. Postoperative outcome was significantly better in TLE-HS group than in the two other groups (p = 0.03 and 0.003). Our study demonstrates that cardinal criteria are reliably helpful to distinguish patients with TLE-HS from those with other TLE and may allow considering TLE-HS as a distinctive syndrome.

Periventricular nodular heterotopia (PNH) is a malformation of cortical development that frequently causes drug-resistant epilepsy. The epileptogenicity of ectopic neurons in PNH as well as their role in generating interictal and ictal activity is still a matter of debate. We report the first in vivo microelectrode recording of heterotopic neurons in humans. Highly consistent interictal patterns (IPs) were identified within the nodules: 1) Periodic Discharges PLUS Fast activity (PD+F), Sporadic discharges PLUS Fast activity (SD+F), and 3) epileptic spikes (ES). Neuronal firing rates were significantly modulated during all IPs, suggesting that multiple IPs were generated by the same local neuronal populations. Furthermore, firing rates closely followed IP morphologies. Among the different IPs, SD+FA pattern was found only in the three nodules that were actively involved in seizure generation, but was never observed in the nodule that did not take part in ictal discharges. On the contrary, PD+F and ES were identified in all nodules. Units that were modulated during the IPs were also found to participate in seizures, increasing their firing rate at seizure onset and maintaining an elevated rate during the seizures. Together, nodules in PNH are highly epileptogenic, and show several IPs that provide promising pathognomonic signatures of PNH. Furthermore, our results show that PNH nodules may well initiate seizures.HighlightsFirst in vivo microelectrode description of local epileptic activities in human PNHRecordings revealed multiple microscopic epileptic interictal patternsFiring rates of all detected units were significantly modulated during all interictal patternsSeizures recruited the same units that are involved in interictal activity

Transthyretin familial amyloid polyneuropathy (FAP) is a rare disease with autosomal transmission due to point mutation of the transthyretin (TTR) gene. It is the most disabling hereditary neuropathy affecting sensory, motor and autonomic nerves, and is irreversible and fatal within 7 to 12 years of onset in the absence of therapy. Diagnosis is usually delayed for 1-5 years because the onset is usually insidious, and a positive family history is lacking in 50% of late-onset cases. Penetrance is variable, and depends of the age of the carrier and age of onset in family members. Two treatments are available: liver transplantation, to suppress the main source of systemic production of mutant TTR; and TTR tetramer stabilizer drugs, to avoid the release of highly amyloidogenic monomers and oligomers. These therapies are able to stop or slow the progression of the disease in its early stages. Genetic counseling is crucial to detect carriers at risk of developing the disease. The European network for TTR-FAP recommends careful baseline assessment by questionnaire, clinical examination and neurophysiological tests, and periodic consultations to detect the onset of disease in time to start anti-amyloid therapy after biopsy findings of amyloid deposition. A therapeutic educational program is important for improving patients' awareness. Patients are considered symptomatic and ill when they themselves perceive symptoms or changes, including changes from baseline measurements on neurophysiological tests, followed by findings of amyloid deposition on biopsy. The most sensitive biopsies are from the labial salivary gland and skin.

In patients with pharmaco-resistant focal epilepsies investigated with intracranial electroencephalography (iEEG), direct electrical stimulations of a cortical region induce cortico-cortical evoked potentials (CCEP) in distant cerebral cortex, which properties can be used to infer large scale brain connectivity. In 2013, we proposed a new probabilistic functional tractography methodology to study human brain connectivity. We have now been revisiting this method in the F-TRACT project (f-tract.eu) by developing a large multicenter CCEP database of several thousand stimulation runs performed in several hundred patients, and associated processing tools to create a probabilistic atlas of human cortico-cortical connections. Here, we wish to present a snapshot of the methods and data of F-TRACT using a pool of 213 epilepsy patients, all studied by stereo-encephalography with intracerebral depth electrodes. The CCEPs were processed using an automated pipeline with the following consecutive steps: detection of each stimulation run from stimulation artifacts in raw intracranial EEG (iEEG) files, bad channels detection with a machine learning approach, model-based stimulation artifact correction, robust averaging over stimulation pulses. Effective connectivity between the stimulated and recording areas is then inferred from the properties of the first CCEP component, i.e. onset and peak latency, amplitude, duration and integral of the significant part. Finally, group statistics of CCEP features are implemented for each brain parcel explored by iEEG electrodes. The localization (coordinates, white/gray matter relative positioning) of electrode contacts were obtained from imaging data (anatomical MRI or CT scans before and after electrodes implantation). The iEEG contacts were repositioned in different brain parcellations from the segmentation of patients' anatomical MRI or from templates in the MNI coordinate system. The F-TRACT database using the first pool of 213 patients provided connectivity probability values for 95% of possible intrahemispheric and 56% of interhemispheric connections and CCEP features for 78% of intrahemisheric and 14% of interhemispheric connections. In this report, we show some examples of anatomo-functional connectivity matrices, and associated directional maps. We also indicate how CCEP features, especially latencies, are related to spatial distances, and allow estimating the velocity distribution of neuronal signals at a large scale. Finally, we describe the impact on the estimated connectivity of the stimulation charge and of the contact localization according to the white or gray matter. The most relevant maps for the scientific community are available for download on f-tract. eu (David et al., 2017) and will be regularly updated during the following months with the addition of more data in the F-TRACT database. This will provide an unprecedented knowledge on the dynamical properties of large fiber tracts in human. he research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013) / ERC Grant Agreement n. 616268 “F-TRACT”. All the computations presented in this paper were performed using the CIMENT infrastructure (https://ciment.ujf-grenoble.fr), which is supported by the Rhône-Alpes region (GRANT CPER07_13 CIRA: http://www.ci-ra.org). We thank Bruno Bzenik and Romain Cavagna for their help on the CIMENT facility, and Jean-François Mangin and Cyril Poupon from Neurospin, CEA Saclay, for providing us with the ARCHI DTI database.

International audience; Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is a heterogeneous syndrome. Surgery results in seizure freedom for most pharmacoresistant patients, but the epileptic and cognitive prognosis remains variable. The 2013 International League Against Epilepsy (ILAE) histopathological classification of hippocampal sclerosis (HS) has fostered research to understand MTLE-HS heterogeneity. We investigated the associations between histopathological features (ILAE types, hypertrophic CA4 neurons, granule cell layer alterations, CD34 immunopositive cells) and clinical features (presurgical history, postsurgical outcome) in a monocentric series of 247 MTLE-HS patients treated by surgery. NeuN, GFAP and CD34 immunostainings and a double independent pathological examination were performed. 186 samples were type 1, 47 type 2, 7 type 3 and 7 samples were gliosis only but no neuronal loss (noHS). In the type 1, hypertrophic CA4 neurons were associated with a worse postsurgical outcome and granule cell layer duplication was associated with generalized seizures and episodes of status epilepticus. In the type 2, granule cell layer duplication was associated with generalized seizures. CD34+ stellate cells were more frequent in the type 2, type 3 and in noHS. These cells had a Nestin and SOX2 positive, immature neural immunophenotype. Patients with nodules of CD34+ cells had more frequent dysmnesic auras. CD34+ stellate cells in scarce pattern were associated with higher ratio of normal MRI and of stereo-electroencephalographic studies. CD34+ cells were associated with a trend for a better postsurgical outcome. Among CD34+ cases, we proposed a new entity of BRAF V600E positive HS and we described three hippocampal multinodular and vacuolating neuronal tumours. To conclude, our data identified new clinicopathological associations with ILAE types. They showed the prognostic value of CA4 hypertrophic neurons. They highlighted CD34+ stellate cells and BRAF V600E as biomarkers to further decipher MTLE-HS heterogeneity. This article is protected by copyright. All rights reserved.

Epilepsy contributes little to road traffic accidents (0.25% of accidents) compared, for instance, to alcohol abuse (at least 30 times higher). Current factors, such as age and sex, or other chronic medical conditions also increase the risk of road traffic accidents but do not carry driving restrictions. So, the European Commission fairly established rules permitting individuals having experienced one or more epileptic seizures to drive if their road accident risk is low. Road accident risk related to epileptic seizures in various clinical situations is evaluated by the driving license commission, mainly with the aid of criteria based on seizure-free periods. A person who has had an epileptic seizure should notify the authorities. He should be advised by treating physician not to drive before. In case of an authorisation, any new relevant event should be notified to the authorities in the course of legal follow-up. Improvements of the current regulations by European data registries are under way.

To delineate the clinical and EEG features of adults with focal epilepsy associated with a generalized paroxysmal fast activity (GPFA) pattern on EEG who developed refractory seizures, notably drop attacks, but do not fulfill the classical triad for the diagnosis of Lennox–Gastaut syndrome (LGS) and provide further insight into LGS mechanisms. Among 957 patients admitted to video-EEG monitoring between 2002 and 2015, we retrospectively research adult patients with refractory focal epilepsy, drop attacks and GPFA on EEG. We collected demographic, anamnestic, and clinical data from medical records. We reviewed for all patients the interictal and ictal video-EEG recordings. We identified ten patients with focal epilepsy and electro-clinical features of LGS. As compared to classical LGS patients, our patients: (1) began epilepsy later (15.4 ± 8 years); (2) exhibited exclusively focal onset seizures, including drop attacks seizures linked to focal asymmetrical tonic posturing seizures; (3) had a stable cognition over time and (4) evolved favourably with a good secondary response to treatments in 80% of cases. Interestingly, all patients exhibited apparent diffuse interictal and ictal EEG abnormalities but a detailed analysis revealed that 50% had asymmetrical GPFA and 70% secondary bilateral synchrony processes. We may hypothesize here that a process of “secondary LGS” occurred which produced a worsening of seizures with the apparition of drop attacks and GPFA on EEG. This study brings arguments to consider that some cases of LGS could be linked to the development of a “secondary epileptic network” driven by a primary focal epileptic zone.

International audience; OBJECTIVE:The reasons for failure of surgical treatment for mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS) remain unclear. This retrospective study analyzed seizure, cognitive, and psychiatric outcomes, searching for factors associated with seizure relapse or cognitive and psychiatric deterioration after MTLE-HS surgery.METHODS:Seizure, cognitive, and psychiatric outcomes were reviewed after 389 surgeries performed between 1990 and 2015 on patients aged 15-67 years at a tertiary center. Three surgical approaches were used: anterior temporal lobectomy (ATL; n = 209), transcortical selective amygdalohippocampectomy (SAH; n = 144), and transsylvian SAH (n = 36).RESULTS:With an average follow-up of 8.7 years (range = 1.0-25.2), seizure outcome was classified as Engel I in 83.7% and Engel Ia in 57.1% of patients. The histological classification of HS was type 1 for 75.3% of patients, type 2 for 18.7%, and type 3 for 1.2%. Two factors were significantly associated with seizure recurrence: past history of status epilepticus and preoperative intracranial electroencephalographic recording. In contrast, neither HS type, the presence of a dual pathology, nor surgical approach was associated with seizure outcome. Risk of cognitive impairment was 3.12 (95% confidence interval = 1.27-7.70), greater in patients after ATL than in patients after transcortical SAH. A presurgical psychiatric history and postoperative cognitive impairment were associated with poor psychiatric outcome.SIGNIFICANCE:The SAH and ATL approaches have similar beneficial effects on seizure control, whereas transcortical SAH tends to minimize cognitive deterioration after surgery. Variation in postsurgical outcome with the class of HS should be investigated further.

In a quest for direct evidence of oscillation entrainment, we analyzed intracerebral electroencephalographic recordings obtained during intracranial electrical stimulation in a cohort of three medication-resistant epilepsy patients tested pre-surgically. Spectral analyses of non-epileptogenic cerebral sites stimulated directly with high frequency electrical bursts yielded episodic local enhancements of frequency-specific rhythmic activity, phase-locked to each individual pulse. These outcomes reveal an entrainment of physiological oscillatory activity within a frequency band dictated by the rhythm of the stimulation source. Our results support future uses of rhythmic stimulation to elucidate the causal contributions of synchrony to specific aspects of human cognition and to further develop the therapeutic manipulation of dysfunctional rhythmic activity subtending the symptoms of some neuropsychiatric conditions. En una búsqueda de evidencia directa de arrastre de oscilación, se analizaron los registros electroencefalográficos intracerebrales obtenidos durante la estimulación eléctrica intracraneal en una cohorte de tres pacientes epilépticos resistentes a la medicación probados prequirúrgicamente. Los análisis espectrales de puntos cerebrales no epileptógenos estimulados directamente con ráfagas eléctricas de alta frecuencia produjeron mejoras episódicas locales de la actividad rítmica específica de frecuencia, bloqueada de fase a cada impulso individual. Estos resultados revelan un arrastre de la actividad oscilatoria fisiológica dentro de una banda de frecuencia dictada por el ritmo de la fuente de estimulación. Nuestros resultados apoyan los usos futuros de la estimulación rítmica para dilucidar las contribuciones causales de la sincronía a aspectos específicos de la cognición humana y para desarrollar aún más la manipulación terapéutica de la actividad rítmica disfuncional que subtiende los síntomas de algunas afecciones neuropsiquiátricas. En una recerca d'evidència directa d'arrossegament d'oscil·lació, es van analitzar els registres electroencefalogràfics intracerebrals obtinguts durant l'estimulació elèctrica intracranial en una cohort de tres pacients epilèptics resistents a la medicació provats prequirúrgicament. Les anàlisis espectrals de punts cerebrals no epileptògens estimulats directament amb ràfegues elèctriques d'alta freqüència van produir millores episòdiques locals de l'activitat rítmica específica de freqüència, bloquejada de fase a cada impuls individual. Aquests resultats revelen un arrossegament de l'activitat oscil·latòria fisiològica dins d'una banda de freqüència dictada pel ritme de la font d'estimulació. Els nostres resultats recolzen els usos futurs de l'estimulació rítmica per dilucidar les contribucions causals de la sincronia a aspectes específics de la cognició humana i per desenvolupar encara més la manipulació terapèutica de l'activitat rítmica disfuncional que subtendeix els símptomes d'algunes afeccions neuropsiquiàtriques.

International audience; BackgroundHippocampal sclerosis is the most common cause of drug-resistant epilepsy amenable for surgical treatment and seizure control. This study aimed to analyze morbidities related to surgery of mesial temporal lobe epilepsy associated with hippocampal sclerosis and to identify possible risk factors for complications.MethodsA retrospective analysis of postoperative complications was made for 389 operations performed between 1990 and 2015 on patients aged 15 to 67 years (mean 36.8). Three surgical approaches were used: anterior temporal lobectomy (ATL) (n=209), transcortical selective amygdalohippocampectomy (SAH) (n=144) and transylvian SAH (n=36). Complications were classified as minor, or major if there was a neurological impairment or if further surgical or medical treatment was needed.ResultsComplications followed 15.4% of operations. They were classed as major for 4.1% of patients, but there were no mortalities. Persistent neurological deficits occurred in 0.5% of patients. In 3 cases (0.8%) additional surgery was needed to treat an intracranial hematoma, a delayed hydrocephalus and a subdural empyema. Symptomatic visual field defects (VFDs) were frequent and included contralateral superior quadrantanopia (8.2%) or hemianopia (1.3%). Overall complications (P=0.04) and symptomatic VFDs (P=0.04) were most frequent in operations on men. Major complications occurred most often with the ATL surgical approach than with transcortical SAH (P=0.03).ConclusionsMajor complications occur rarely after mesial temporal surgery on epileptic patients. They occur more often following ATL than transcortical SAH approach. Complications tend to be temporary with symptoms of limited duration for surgery performed by experienced teams on carefully selected and evaluated patients.Key Words

Voluntary control of oscillatory activity represents a key target in the self-regulation of brain function. Using a real-time closed-loop paradigm and simultaneous macro- and micro-electrode recordings, we studied the effects of self-induced intracortical oscillatory activity (4–8 Hz) in seven neurosurgical patients. Subjects learned to robustly and specifically induce oscillations in the target frequency, confirmed by increased oscillatory event density. We have found that the session-to-session variability in performance was explained by the functional long-range decoupling of the target area suggesting a training-induced network reorganization. Downstream effects on more local activities included progressive cross-frequency-coupling with gamma oscillations (30–120 Hz), and the dynamic modulation of neuronal firing rates and spike timing, indicating an improved temporal coordination of local circuits. These findings suggest that effects of voluntary control of intracortical oscillations can be exploited to specifically target plasticity processes to reconfigure network activity, with a particular relevance for memory function or skill acquisition.

Objective To compare the performance of 4h-video EEG monitoring (VEEG) and 1h-nap-VEEG in an Epileptology Unit. Methods We examined short-term VEEG data from 196 patients admitted to characterize their: (i) clinical events; (ii) epileptic syndromes or (iii) state after status epilepticus or surgery. We compared the 4h-VEEG and 1h-nap-VEEG performances using three measures: (i) the capability to detect epileptic seizures (ES), psychogenic non-epileptic seizures (PNES), interictal epileptiform abnormalities (IEA) and sleep-related IEA; (ii) the usefulness to answer questions on referral; (iii) the sensitivity for the final diagnosis. Results The 4h-VEEG test recorded clinical events in 53.6% of 196 patients, IEA in 41.3%, sleep-related IEA in 34.7%, and was judged as useful in 66.8%. The 4h-VEEG was compared to the 1h-nap-VEEG in 129 patients. 4h-VEEG had a better capability to record clinical events (50.3% vs. 6.2%, p usefulness (63.5% vs . 37.2%, p sensitivity for both ES (69.3% vs. 49.3%, p =0.0035) and PNES (61.3% vs. 15.4%, p =0.0014) than nap-EEG. Conclusions This work found 4h-VEEG records were superior to the 1h-nap-VEEG test on the basis of three complementary measures, capability, usefulness and sensitivity. Significance 4h-VEEG is a useful alternative investigation tool in an Epileptology Unit.

From the very beginning the seizure prediction community faced problems concerning evaluation, standardization, and reproducibility of its studies. One of the main reasons for these shortcomings was the lack of access to high-quality long-term electroencephalography (EEG) data. In this article we present the EPILEPSIAE database, which was made publicly available in 2012. We illustrate its content and scope. The EPILEPSIAE database provides long-term EEG recordings of 275 patients as well as extensive metadata and standardized annotation of the data sets. It will adhere to the current standards in the field of prediction and facilitate reproducibility and comparison of those studies. Beyond seizure prediction, it may also be of considerable benefit for studies focusing on seizure detection, basic neurophysiology, and other fields.

Epilepsy, a neurological disorder in which patients suffer from recurring seizures, affects approximately 1% of the world population. In spite of available drug and surgical treatment options, more than 25% of individuals with epilepsy have seizures that are uncontrollable. For these patients with intractable epilepsy, the unpredictability of seizure occurrence underlies an enhanced risk of sudden unexpected death or morbidity. A system that could warn the patient of the impending event or trigger an antiepileptic device would dramatically increase the quality of life for those patients. Here, we proposed a patient-specific algorithm for possible seizure warning using machine learning classification of 34 algorithmic features derived from EEG–ECG recordings. We evaluated our algorithm on unselected and continuous recordings of 12 patients (total of 108 seizures and 3178-h). Good out-of-sample performances were observed around 25% of the patients with an average preictal period around 30 min and independently of the EEG type (scalp or intracranial). Inspection of the most discriminative EEG–ECG features revealed that good classification rates reflected specific physiological precursors, particularly related to certain stages of sleep. From these observations, we conclude that our algorithmic strategy enables a quantitative way to identify “pro-ictal” states with a high risk of seizure generation.

A 69-year-old woman had insomnia, restless legs syndrome, and violent movements during sleep; she had had a generalized seizure several years previously. She underwent 4 days of video-EEG investigation for these movements (table, and figure e-1 on the Neurology ® Web site at [Neurology.org][1]). There was no epileptic activity, but repetitive, stereotyped movements (88 movements/hour; movement duration: 2.5 seconds) occurred only during sleep, which were typical of periodic leg movements but associated with atypical, polyphasic hand cycling/rubbing movements (see video). This complex motor pattern might be confused with a focal epileptic seizure. [1]: http://neurology.org/lookup/doi/10.1212/WNL.0000000000002224

International audience; PURPOSE: Idiopathic generalized epilepsies (IGE) are age-related epileptic syndromes mainly described in children and adolescence. Our aim is to describe their electroclinical features in the elderly. METHODS: Patients aged 70 years or more were prospectively selected in a geriatric EEG laboratory on the basis of rhythmic generalized spikes and waves discharges. Their clinical data were then examined to ascertain the syndromic diagnosis. RESULTS: Among 1181 geriatric patients referred for EEG over a 30-month period, IGE were identified in 10 cases. Eight patients began seizures in childhood or adulthood (3 childhood absence epilepsies, 2 juvenile/adult myoclonic epilepsies and 3 epilepsies with-generalized-tonic-clonic-seizures alone (EGTCS)) and 2 very late in life with EGTCS. The early-onset IGE cases had usually experienced a quiescent long period in adulthood before relapsing late in life. This relapse, mostly severe, consisted of absence status, myoclonic status or repeated generalized tonic clonic seizures and was often not-situation related. Absence status and myoclonic status were stopped by Clonazepam. The two late-onset IGE cases had familial history of epilepsy. Inappropriate antiepileptic drugs (AED) previously given in four patients with two worsenings were corrected. CONCLUSIONS: In this study, the non-negligible number of elderly cases observed over a short period of time suggests that IGE are frequent in the elderly but underestimated until recently. IGE may be lifelong with late severe exacerbations. A few very late-onset IGE cases exist. EEG remains useful in contributing to diagnose IGE and AED adjustment continues to be beneficial at extreme age.

International audience; Invasive electroencephalography recordings with depth or subdural electrodes are necessary to identify the ictogenic area in some drug-resistant focal epilepsies. We aimed to analyze the safety profile of intracranial electrode implantation in a tertiary center and the factors associated with its complications. We retrospectively examined complications in 163 intracranial procedures performed in adult patients. Implantation methods included oblique depth stereotactic approach (n = 128) and medial-temporal depth stereotactic approach in combination with subdural strip placement (n = 35). 1201 depth macroelectrodes, 59 bundles of microelectrodes (in 30 patients) and 148 subdural electrodes were implanted. Complications were classified as major (requiring treatment or leading to neurological impairment) or minor. The rate of overall complications was 4.9 % (n = 8), with 3.1 % (n = 5) of major complications, though no permanent morbidity or mortality was recorded. Infection occurred in 1.2 % and hemorrhage in 3.7 % of patients. One hemorrhage occurred for every 225 electrodes implanted (4.4 ‰). Microelectrodes were not responsible for any complications. Overall and hemorrhagic complications were significantly associated with MRI-negative cases (7.3 and 6.3 % versus 0 %, p = 0.04). We believe that intracranial electrode implantation has a favorable safety profile, without permanent deficit. These risks should be balanced with the benefits of invasive exploration prior to surgery. Furthermore, this study provides preliminary evidence regarding the safety of micro-macroelectrodes.

International audience; Analysing the clinical characteristics of seizures constitutes a fundamental aspect of the presurgical evaluation of patients with medial temporal lobe epilepsy and unilateral hippocampal sclerosis (MTLE-HS), the most frequent form of focal epilepsy accessible to surgery. We sought to retrospectively determine whether objective manifestations could have a reliable lateralizing value in a large population of MTLE-HS patients and if their presence could help to identify those patients who would be seizure free after surgery. We analysed the frequency and predictive lateralizing value of objective ictal and postictal signs in 391 patients with MTLE-HS (183 left/208 right). Data were derived from chart review and not from blinded videoEEG analysis. Correlation between the presence of reliable lateralizing signs and postoperative outcome was performed in a subgroup of 302 patients who underwent surgery. Contralateral dystonic posturing was the most frequent and reliable lateralizing sign that correctly lateralized the focus in 96% of patients. Unilateral head/eye deviation was noted in 42% of the patients and predicted unilateral focus in 67%. Ipsilateral postictal nose wiping, contralateral clonus and hypokinesia correctly lateralized the focus in 75%, 81%, respectively, and 100 of patients but were less frequently depicted. Postictal aphasia was a strong lateralizing sign for left MLE-HS. The presence of reliable lateralizing signs was not a predictor of seizure freedom. Seizure semiology is a simple tool that may permit reliable lateralization of the seizure focus in MTLE-HS. The presence of reliable lateralizing signs is not associated with a better postoperative outcome.

Summary: Purpose: To assess the seizure-freedom rates and self-perceived psychosocial changes associated with the long-term outcome of epilepsy surgery in patients with refractory medial temporal lobe epilepsy associated with hippocampal sclerosis. Methods: A standard questionnaire was given to 183 patients who underwent surgery between 1988 and 2004, and 110 were completed. Results: The mean duration of follow-up after surgery was 7 years, with a maximum of 17 years. The probability that patients were seizure-free after surgery was dependent on the definition of the seizure freedom. For the patients who were seizure-free since surgery (Engel's class Ia), the probability was 97.6% at 1 year after surgery, 85.2% at 2 years after surgery, 59.5% at 5 years after surgery, and 42.6% at 10 years after surgery. For the patients who still experienced rare disabling seizures after surgery but were seizure-free at least 1 year before the time of assessment, the probability was of 97.6% at 1 year after surgery, 95% at 2 years after surgery, 82.8% at 5 years after surgery, and 71.1% at 10 years after surgery. The psychosocial long-term outcome, as measured by indices of driving, employment, familial and social relationships, and marital status, was similar to the psychosocial short-term outcome. It did not depend on seizure freedom or on follow-up time interval and was not influenced statistically by seizure frequency in cases of persisting seizures. Most but not all patients noticed a substantial overall improvement in their psychosocial condition; 48% drove (increased by 7%), 47% improved (14% worsened) in their employment status, and 68% improved (5% worsened) in their familial and social relationships. Overall, 91% of patients were satisfied with the surgery, and 92% did not regret their decision. Conclusions: The results of this study suggest that temporal lobe surgery has real long-term benefits. Two specific conclusions emerge: (a) the long-term rates of freedom from seizure depend on how seizure freedom is defined, and (b) the psychosocial long-term outcome does not change dramatically over years and does not depend on seizure freedom.

SummaryModels of the “visual word form system” postulate that a left occipitotemporal region implements the automatic visual word recognition required for efficient reading. This theory was assessed in a patient in whom reading was explored with behavioral measures, fMRI, and intracranial local field potentials. Prior to surgery, when reading was normal, fMRI revealed a normal mosaic of ventral visual selectivity for words, faces, houses, and tools. Intracranial recordings demonstrated that the left occipitotemporal cortex responded with a short latency to conscious but also to subliminal words. Surgery removed a small portion of word-responsive occipitotemporal cortex overlapping with the word-specific fMRI activation. The patient developed a marked reading deficit, while recognition of other visual categories remained intact. Furthermore, in the post-surgery fMRI map of visual cortex, only word-specific activations disappeared. Altogether, these results provide direct evidence for the causal role of the left occipitotemporal cortex in the recognition of visual words.

PURPOSE: Ictal single-photon emission computed tomography (SPECT) may help localize the seizure-onset zone (SOZ) by detecting changes in regional cerebral blood flow induced by epileptic discharges. This imaging method also reveals hyperperfusions in areas of seizure propagation, including the hemisphere contralateral to the SOZ. We have studied the occurrence, the topography, and the clinical value of such contralateral ictal hyperperfusion areas (HPAs). METHODS: We examined data from presurgical evaluations of 36 consecutive patients with pharmacoresistant partial epilepsy of various localizations. Ictal and interictal SPECT examinations were made with 99mTc-ECD, and the scans were processed for coregistration, normalization, subtraction, and merging with MRI images. RESULTS: Contralateral HPAs were observed in 72% of the patients: 50% of mesiotemporal epilepsy cases with hippocampal sclerosis, 85.7% of the other mesiotemporal epilepsies, 85.7% of neocortical lateral temporal epilepsies, and 87.5% of extratemporal epilepsies. Contralateral HPAs were usually symmetrical to the SOZ, forming a mirror image, observed in 57.1% of the patients. They could be slightly asymmetrical in mesiotemporal epilepsies, perhaps because of the particular anatomic pathways linking temporal lobes. In neocortical epilepsies, they were located in the cortex homotopic to the SOZ. CONCLUSIONS: We show that the symmetrical nature of the mirror image usually does not disturb SPECT interpretation. It can confirm the location of the SOZ (11 patients) and even occasionally improve the precision of its definition (nine patients) by restraining several potential SOZ-related HPAs to a single one or by permitting a restricted localization of the SOZ in a large HPA.

Obstructive sleep apnea (OSA) is common in patients with refractory epilepsy and may exacerbate seizures. In epileptic patients with OSA, seizures occur more frequently during sleep. Seizure frequency may be reduced by treating OSA and increase if the treatment is interrupted or neglected. It is not clear how OSA provokes seizures. Multiple seizureprovoking factors including cerebral hypoxemia, sleep deprivation and sleep fragmentation might be involved. The temporal link between OSA and seizures or interictal events might be better understood with careful analysis of video EEG (vEEG) records. Such data has never been precisely reported. We report here a direct relation between OSA and both ictal and interictal epileptic events during vEEG investigations in a patient with 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.

The authors conducted an open study of levetiracetam as add-on therapy in nine patients with well-defined progressive myoclonic epilepsies and refractory myoclonus. Myoclonus was evaluated semiquantitatively (territory, intensity, daily living activities). Five patients had improvement of their myoclonus score. Levetiracetam may benefit myoclonus in progressive myoclonic epilepsy.

Introduction The frequency of local oscillations and inter-regional synchrony has been correlated with the engagement of cognitive operations. Notwithstanding, adding causality to these associations requires the direct manipulation of brain rhythms Noninvasive stimulation with single pulses of TMS coupled to scalp-EEG recordings has provided evidence of local increases in power at specific frequency bands, likely to reflecting the local “natural” frequencies as defined by Rosanova et al. (2009). Mapping of these phenomena across human brain areas is paramount for understanding the neural coding mechanisms involved in information transfer and to further develop the use of exploratory and therapeutic neuromodulation. Objectives Mapping the human anatomical and physiological causal features of spreading natural oscillations across brain regions by co-localizing an atlas of structural connectivity with a map of functional interactions based on the distribution of rhythmic activity enabled by intracortical stimulation. Methods We analyzed intracranial EEG signals from 8 epilepsy patients implanted with depth multielectrodes in frontal, prefrontal, parietal and temporal areas, the amygdala and the hippocampus. We analyzed in the frequency-domain oscillatory activity elicited by single electrical pulses delivered through pairs of adjacent contacts, as recorded by the remaining contacts, and modeled a map of effective connectivity. Individual anatomical maps of white matter fasciculi were tracked individually and co-localized with the former. Results Single electrical pulses induced frequency-specific modulations of power in contacts not employed to deliver the pulses. Oscillatory enhancements were influenced by both the local anatomical environment and the estimated probability of white matter connections between stimulated and recorded sites. Conclusions Our results support the feasibility of studying functional connectivity patterns by analyzing the local induction and network spread of natural oscillation frequencies, enabled by single pulses of intracranial stimulation and to co-register them with white matter connectivity maps. This approach might contribute to the compilation whole-brain connectivity atlases able to categorize oscillation frequency to behavioral relationships throughout brain regions and their connections in humans.

International audience; Background and purpose : Medial temporal lobe epilepsy with unilateral hippocampal sclerosis (MTLE-HS) is the most frequent form of surgical temporal lobe epilepsy. In this study, it was aimed to determine whether different types of aura represent a cardinal and characteristic feature of MTLE-HS and might provide a diagnostic complement to help identify patients who will be seizure-free after surgery.Methods : All types of auras and associations of auras reported by 400 MTLE-HS patients referred for surgery were retrospectively collected and their statistical correlation with the postoperative outcome was examined in a subgroup of 305 patients who underwent surgery.Results : A total of 876 auras were collected, classified into 12 categories. Globally, MTLE-HS patients reported widely variable auras and groupings of auras. Most common were autonomic and abdominal visceral auras, followed by psychoaffective and experiential auras; less common, but seen in 10%–15% of patients, were non-specific auras, somatosensory auras and visual auras, and least common, reported by less than 10% of patients, were auditory, gustatory, vestibular, olfactory and intellectual auras. No auras were reported in 10% of patients. 65% of patients experienced more than one type of aura (two to seven). No specific groupings of aura type were apparent. No evidence was found for correlation between postoperative outcome and (i) any category of aura, (ii) the number of categories of aura per patient and (iii) any association of categories of auras.Conclusion : Auras and association of auras vary widely in MTLE-HS and provide no useful insight into surgical outcome.

Summary Background New methods derived from non-linear analysis of intracranial recordings permit the anticipation of an epileptic seizure several minutes before the seizure. Nevertheless, anticipation of seizures based on standard scalpelectroencephalographical (EEG) signals has not been reported yet. The accessibility to preictal changes from standard EEGs is essential for expanding the clinical applicability of these methods. Methods We analysed 26 scalp-EEG/video recordings, from 60 min before a seizure, in 23 patients with temporal-lobe epilepsy. For five patients, simultaneous scalp and intracranial EEG recordings were assessed. Long-term changes before seizure onset were identified by a measure of non-linear similarity, which is very robust in spite of large artifacts and runs in real-time. Findings In 25 of 26 recordings, measurement of non-linear changes in EEG signals allowed the anticipation of a seizure several minutes before it occurred (mean 7 min). These preictal changes in the scalp EEG correspond well with concurrent changes in depth recordings. Interpretation Scalp-EEG recordings retain sufficient dynamical information which can be used for the analysis of preictal changes leading to seizures. Seizure anticipation strategies in real-time can now be envisaged for diverse clinical applications, such as devices for patient warning, for efficacy of ictal-single photon emission computed tomography procedures, and eventual treatment interventions for preventing seizures.

Recent studies have shown that non-linear analysis of intracranial activities can detect a ‘pre-ictal phase’ preceding the epileptic seizure. Nevertheless, the dynamical nature of the underlying neuronal process and the spatial extension of this pre-ictal phase still remain unknown. In this paper, we address these aspects using a new non-linear measure of dynamic similarity between different parts of intracranial recordings of nine patients with medial temporal lobe epilepsy recorded during transitions to seizure. Our results confirm that non-linear changes in neuronal dynamics allow, in most cases (16 out of 17), a seizure anticipation several minutes in advance. Furthermore, we show that the spatial distribution of pre-ictal changes often involves an extended network projecting beyond the limits of the epileptogenic region. Finally, the pre-ictal phase could frequently (13 out of 17) be characterized with a marked shift toward slower frequencies in upper delta or theta frequency range.

The degree of interdependence between intracranial electroencephalographic (EEG) channels was investigated in epileptic patients with temporal lobe seizures during interictal (between seizures) periods. With a novel method to characterize nonlinear cross-predictability, that is, the predictability of one channel using another channel as data base, we demonstrated here a possibility to extract information on the spatio-temporal organization of interactions between multichannel recording sites. This method determines whether two channels contain common activity, and often, whether one channel contains activity induced by the activity of the other channel. In particular, the technique and the comparison with surrogate data demonstrated that transient large-scale nonlinear entrainments by the epileptogenic region can be identified, this with or without epileptic activity. Furthermore, these recurrent activities related with the epileptic foci occurred in well-defined spatio-temporal patterns. This suggests that the epileptogenic region can exhibit very subtle influences on other brain regions during an interictal period and raises the possibility that the cross-predictability analysis of interictal data may be used as a significant aid in locating epileptogenic foci.

We investigated the prognostic value of the type of epilepsies and epileptic syndromes for seizure recurrence. In patients with partial epilepsy, we focused on the prognostic value of any structural brain abnormality and of the location of the epileptogenic region.A total of 2,200 adult outpatients were included in a hospital-based observational survey, with a follow-up of 1 to 7 years. Twenty-two percent of the patients exhibited generalized epilepsy, 62% partial epilepsy, and 16% undetermined epilepsy.Seizure control (1 year without seizure) was achieved in 82% of patients who had idiopathic generalized epilepsy, 35% of those with symptomatic partial epilepsy, 45% of those with cryptogenic partial epilepsy, and 11% of those with partial epilepsy associated with hippocampal sclerosis (HS). Temporal lobe epilepsy (TLE) was the most refractory partial epilepsy, with only 20% of such patients remaining seizure free, compared with 36% of extra-TLE patients. In partial epilepsy, HS, cerebral dysgenesis, and dual pathology (HS and another lesion) were associated with a low rate of seizure-free patients (11%, 24%, and 3%, respectively). No significant difference in seizure control was found between patients with extra-TLE and those with TLE and no HS.In adults, partial epilepsy is more difficult to treat than idiopathic generalized epilepsy. In patients who have partial epilepsy, the location of the epileptogenic zone does not seem to be a determining factor. Brain abnormalities--especially HS, either alone or associated with another lesion--are a major prognostic factor.

Epileptic seizures are a principal brain dysfunction with important public health implications, as they affect 0.8% of humans. Many of these patients (20%) are resistant to treatment with drugs1. The ability to anticipate the onset of seizures in such cases would permit clinical interventions. The view of chronic focal epilepsy now is that abnormally discharging neurons act as pacemakers to recruit and entrain other normal neurons by loss of inhibition and synchronization into a critical mass2. Thus, pre-ictal changes should be detectable during the stages of recruitment. Traditional signal analyses, such as the count of focal spike density3, the frequency coherence4 or spectral analyses are not reliable predictors. Non-linear indicators may undergo consistent changes around seizure onset5,6,7. Our objective was to follow the transition into seizure by reconstructing intracranial recordings in implanted patients as trajectories in a phase space and then introduce non-linear indicators to characterize them8,9. These indicators take into account the extended spatio–temporal nature of the epileptic recruitment processes10 and the corresponding physiological events governed by short-term causalities in the time series. We demonstrate that in most cases (17 of 19), seizure onset could be anticipated well in advance (between 2–6 minutes beforehand), and that all subjects seemed to share a similar 'route' towards seizure.

The degree of interdependence between intracranial EEG channels was investigated in four epileptic patients with complex partial seizures of mesial temporal lobe origin. With a new method to characterize nonlinear dynamical interdependence-the mutual nonlinear prediction-we demonstrated here a possibility to quantify, during epileptic seizures, the relationships between EEG signals of electrode contacts in the epileptogenic area. During the interictal period, the degree of nonlinear interdependences were very low or absent. In contrast, it was found that transient patterns of nonlinear interdependences emerge at the initial spread of the seizure, during essential parts of its development, and at seizure end, but the maintenance of these interactions are not observed throughout the seizure activity. These results suggest that the nonlinear associations plays an important role in epileptogenesis, and that the process of neuronal entrainment during seizure onset involves a transient interaction between a distributed network of neuronal aggregates, but the maintenance of this interaction is not required for sustained seizure activity. Furthermore, this technique can describe properly the spatio-temporal organisation of the seizures of medio-temporal lobe origin and could become a very useful tool to aid the localization of the epileptogenic regions at the origin of epileptic seizures and their pathways of propagation.

Seizures associated with toothbrushing have been reported in patients with precentral or postcentral partial epilepsy. Seizures precipitated by thinking have been described in patients with idiopathic generalized epilepsy. We report a patient with intractable partial epilepsy in which seizures were induced both by toothbrushing, and by seeing or thinking about toothbrush and toothpaste. Video-EEG analysis revealed a left temporal lobe origin for these reflex seizures. We discuss how complex multimodal stimuli may trigger these reflex seizures.

This study includes 11 patients (3 males, 8 females) with mean age of 29 years (range: 15-42 years) who underwent a presurgical evaluation for refractory complex partial seizures (CPS). In all patients, neuroimaging (1.5 T optimum-MR) demonstrated intracranial structural abnormalities (space-occupying: n = 2; atrophic: n = 8; dysplastic: n = 1) and video-EEG monitoring showed CPS, because of discrepancies in the non-invasive examinations, all underwent additional intracranial EEG monitoring. After tailored resective procedures, all but one patient became seizure free. Mean follow-up was 30 months (range: 12-52 months). Results of intracranial EEG recording were compared with spatiotemporal dipole mapping of interictal and ictal epileptic discharges. Interictal dipole modelling revealed two distinct dipole patterns. Patients with lesions located in the medial temporal lobe uniformly presented a combined dipole that consisted of a radial and a tangential component with a high degree of elevation relative to the axial plane. Patients with extrahippocampal lesions had a less stable dipole with a predominant radial component. Dipole modelling of early ictal discharges revealed a striking correspondence with the interictal findings in individual patients. Elevation of ictal dipoles was always congruent with localisation based on intracranial EEG recordings. Interictal and ictal dipole mapping of medial temporal lobe sources may limit the number of surgical candidates for refractory CPS that need intracranial EEG recording. Whether ictal dipole modelling can be equally useful in extratemporal epilepsy remains to be proven.

We studied subdural recordings from a patient with an unusually focal and stable occipito-temporal epileptic discharge under four experimental conditions. The series of time intervals between successive spike discharges displayed a few (3-5) clusters of periodic values representing statistically significant short-term periodicities when tested against surrogate data. This short-term predictability was modulated during the different experimental conditions by periodicity shifts of the order of 15-30 ms. Correspondingly, there was an increased gamma-band (30-70 Hz) coherence between the epileptic focus and surrounding recording sites. We conclude that the focal epileptic activity is part of an extended network of neural activities which exert a fast modulation reflected in changes of transiently periodic activities.

Summary: Purpose: The validity and clinical significance of dipole modeling in epilepsy surgery candidates is not fully established. Patients and Methods: Interictal and ictal dipole modeling was performed in 43 patients with refractory complex partial seizures (CPS) and intracranial structural abnormalities demonstrated with optimum magnetic resonance imaging (MRI: space–occupying, n = 15; atrophic, n = 26; dysplastic, n = 2). Video–EEG monitoring showed CPS in all patients. In 12 patients, additional intracranial EEG monitoring demonstrated hippocampal seizure onset in 11 patients and medial occipital ictal onset in 1. Results: Spatiotemporal dipole mapping of averaged interictal spikes and epochs of early ictal discharges revealed two distinct dipole patterns. Patients with lesions located in the medial (± lateral) temporal lobe (n = 34) and medial occipital lobe (n = 1) uniformly presented a combined interictal dipole that consisted of a radial and a tangential component with a high degree of elevation relative to the axial plane. Eight of 9 patients with extratemporal lesions had a less stable dipole with a predominant radial component. Ictal dipole modeling identified the ictal onset zone correctly as compared with intracranial EEG recordings from bilateral hippocampal depth electrodes. Ictal dipoles showed a striking correspondence with the interictal dipoles in individual patients. Conclusions: Interictal and ictal dipole mapping provided additional, reliable, and relevant localizing information in surgical candidates for refractory CPS. Ictal dipole analysis may limit the number of patients who require intracranial electrodes.

Recent evidence suggests that some seizures are preceded by preictal changes that start from minutes to hours before an ictal event. Nevertheless an adequate statistical evaluation in a large database of continuous multiday recordings is still missing. Here, we investigated the existence of preictal changes in long-term intracranial recordings from 53 patients with intractable partial epilepsy (in total 531 days and 558 clinical seizures). We describe a measure of brain excitability based on the slow modulation of high-frequency gamma activities (40–140 Hz) in ensembles of intracranial contacts. In prospective tests, we found that this index identified preictal changes at levels above chance in 13.2% of the patients (7/53), suggesting that results may be significant for the whole group (p < 0.05). These results provide a demonstration that preictal states can be detected prospectively from EEG data. They advance understanding of the network dynamics leading to seizure and may help develop novel seizure prediction algorithms.

International audience; Ictal bradycardia and ictal asystole (IA) are rare but severe complications of epileptic seizures. They are difficult to recognize within a seizure and their consequences remain unclear. Herein we aimed to extend the description of electrical and clinical features of seizures with IA and/or syncope. Among 828 patients with epilepsy who were admitted for presurgical video-electroencephalogram (EEG) monitoring evaluation between 2003 and 2012, we selected those presenting IA and/or syncope. We studied the electroclinical sequence of these manifestations and their correlation with electrocardiogram (ECG), and we compared seizures with or without IA among the same patients. Nine (1.08%) of 828 patients (four men, mean age 43 ± 6 years) showed IA. Six patients had temporal lobe epilepsy and the others had frontal, temporooccipital, or occipital epilepsy, demonstrated by intracranial EEG in two. In these patients, 59 of 103 recorded seizures induced a reduction of heart rate (HR), leading to IA in 26. IAs were mostly (80%) symptomatic, whereas ictal HR decreases alone were not. In seizures with IA, we identified usual ictal symptoms, and then symptoms related primarily to cerebral hypoperfusion (pallor, atonia, early myoclonic jerks, loss of consciousness, hypertonia, and fall) and secondarily to cerebral reperfusion (skin flushing, late myoclonic jerks). At 32 ± 18 s after the onset of the seizure, the HR decreased progressively during 11 ± 6 s, reaching a sinusal pause for 13 ± 7 s. The duration of the IA was strongly correlated with electroclinical consequences. IA was longer in patients with atonia (14.8 ± 7 vs. 5.7 ± 3 s), late myoclonic jerks (15.8 ± 7 vs. 8 ± 6 s), hypertonia (19 ± 4.5 vs. 8.3 ± 5 s), and EEG hypoperfusion changes (16 ± 5.6 vs. 6.9 ± 5.5 s). IA may induce a fall during atonia or hypertonia. Surface and intracerebral EEG recordings showed that ictal HR decrease and IA often occurred when seizure activity became bilateral. Finally, we identified one patient with ictal syncopes but without IA, presumably related to vasoplegia. We provide a more complete description of the electroclinical features of seizures with IA, of the mechanism of falls, and distinguish between hypoperfusion and reperfusion symptoms of syncope. Identification of the mechanisms of syncope may improve management of patients with epilepsy. A pacemaker can be proposed, when parasympathetic activation provokes a negative chronotropic effect that leads to asystole. It is less likely to be useful when vasoplegic effects predominate.

Introduction - To evaluate the homogeneity of patients operated on for MTLE. Material and methods - 30 consecutive patients prospectively investigated with clinical, EEG, neuropsychology, MRI, FDG-PET criteria and eventually intracranial EEG, who underwent antero-medial temporal resection (follow-up : 24 months). Results - Clear and well-lateralised MTLE was non-invasively ascertained in 22 patients (73%). Eight patients (27%) had a less pure presentation due to divergent scalp EEG features (bitemporal, widespread or extratemporal), unusual auras or absence of MRI-based hippocampal sclerosis or FDG-PET hypometabolism. They were explored by invasive monitoring which confirmed medial temporal origin of seizures. Outcome was excellent in 95% of the pure cases (Engel's class I) and less favorable in the more difficult ones (65% of class I). Conclusions - MTLE criteria, including the strong contribution of brain imaging, permit to select accurately a large percentage of patients. However a consistant number of patients present a less pure presentation suggesting more complex epileptogenic networks.

We examined the prognostic value of spatial and temporal characteristics of intracerebral propagation of seizures during temporal lobe epilepsy (TLE) surgery. Seven TLE patients resistant to standard anterotemporal lobectomy who had no known causes of resistance [e.g., extratemporal (ET), lesions, multifocal epilepsy] were matched with 7 seizure-free patients and 7 others who were almost seizure-free after operation. Intracerebral ictal propagation pathways were not different in the three groups. Propagation was multidirectional, most frequently to the frontal lobes and sometimes to the contralateral temporal lobe (CTL). ET propagation delays were significantly shorter in resistant patients than in markedly improved patients. The resistant group also had more frequent propagation delays1.0 s, but propagation times1.0 s were equally likely in all groups. The extent of ET propagation and frequency of focal onsets were not different among the groups. Results suggest that very short propagation times predict reduced efficacy of operation, and that long propagation times are not related to surgical success.

Objective: To determine the occurrence of magnetic resonance imaging-detected hippocampal atrophy (HA) in patients with partial epilepsy (temporal and extratemporal, cryptogenic, or symptomatic). Magnetic resonance imaging-detected HA has been demonstrated to be both sensitive and specific for hippocampal sclerosis in cryptogenic temporal lobe epilepsy. Design: Patients' hippocampal formations were measured on a computerized system using Tl-weighted, 5-mm contiguous magnetic resonance coronal images made perpendicular to the hippocampus long axis. Hippocampal atrophy was defined on the basis of a normative asymmetry index and correlated with the epileptogenic focus defined by clinical, electroencephalographic, and magnetic resonance imaging (apart from HA) localizing data. Patients and Control Subjects: Seventy patients with intractable complex partial seizures of temporal, extratemporal, or undefined origin and 21 healthy control subjects. Results: Hippocampal atrophy was present in 70% of patients with cryptogenic temporal lobe epilepsy (TLE) (n=40), 44% of patients with symptomatic TLE (n=9), 29% of patients with extratemporal epilepsy (n=14), and 6% of unclassified patients (n=16). In the cryptogenic TLE category, HA was marked and usually concordant (93%) with electroencephalographic lateralization. Hippocampal atrophy was often mild in the extratemporal epilepsy category. With the use of a wider confidence interval (±3.1 SD instead of ±2.2 SD), HA specificity for TLE increased to 93%, HA specificity for lateralizing cryptogenic TLE reached 96%, and HA sensitivity for cryptogenic TLE stood almost unchanged (68%). We found a link between early convulsions and HA occurrence. Conclusions: Hippocampal atrophy is a marker for TLE. Dual pathologic findings are detected in 44% of symptomatic TLE cases. Mild HA is rarely associated with extratemporal epilepsy. Magnetic resonance imaging-based hippocampal volumetric analysis is a useful method to localize the origin of partial complex seizures.

International audience; Surgical outcome in patients with nonlesional refractory partial epilepsies could be improved by a more precise definition of the epileptogenic zone (EZ). The value of interictal FDG-PET hypometabolism, voxel-based-morphometry (VBM) and diffusion tensor imaging (DTI) is still debated. We compared the sensitivity and specificity of these noninvasive techniques in localizing the EZ with stereo-electroencephalography (SEEG) results. Twenty patients with nonlesional partial epilepsy (13 temporal lobe epilepsy (TLE) and 7 extra-temporal (extra-TLE)) underwent structural MRI, DTI and FDG-PET. FDG-PET was analyzed visually (vPET) blinded and unblinded and by statistical parametric mapping (SPM) (sPET). Individual modifications of grey matter volume and mean diffusivity increase were compared to a control group with SPM. The best sensitivity was provided by vPET unblinded (75%) and the best specificity (60%) by DTI. The sensitivity of vPET blinded (55%) was lower and those of sPET (40%) and VBM (35%) were still lower. In TLE, vPET analyzed either blinded or unblinded, performed the best and additional use of the other tools improved slightly the sensitivity. For extra-TLE, combining vPET and DTI results increased the number of pertinent abnormalities detected especially for circumscribed changes in frontal lobe epilepsy (FLE). Combining vPET and DTI was the more efficient strategy for extra-TLE, allowing the detection of pertinent abnormalities in FLE when FDG-PET alone was not contributive. Combining sPET or VBM with vPET was less useful.

International audience; The mechanisms involved in the transition to an epileptic seizure remain unclear. To examine them, we used tissue slices from human subjects with mesial temporal lobe epilepsies. Ictal-like discharges were induced in the subiculum by increasing excitability along with alkalinization or low Mg(2+). During the transition, distinct pre-ictal discharges emerged concurrently with interictal events. Intracranial recordings from the mesial temporal cortex of subjects with epilepsy revealed that similar discharges before seizures were restricted to seizure onset sites. In vitro, pre-ictal events spread faster and had larger amplitudes than interictal discharges and had a distinct initiation site. These events depended on glutamatergic mechanisms and were preceded by pyramidal cell firing, whereas interneuron firing preceded interictal events that depended on both glutamatergic and depolarizing GABAergic transmission. Once established, recurrence of these pre-ictal discharges triggered seizures. Thus, the subiculum supports seizure generation, and the transition to seizure involves an emergent glutamatergic population activity.

International audience; This study aimed at determining if the recovery of mean diffusivity (MD) in the contralateral non sclerotic hippocampus is correlated with a change in memory outcome after surgery in patients with medial temporal lobe epilepsy (MTLE). Verbal and non-verbal memory scores and MD were assessed in 23 patients with MTLE before and after surgical treatment of epilepsy. The recovery of MD in the left hippocampus was correlated with the performance on verbal memory tests, and the recovery of MD in all patients was correlated with the performance on non-verbal memory tests. This finding strengthens the hypothesis that reversible diffusion abnormalities in the contralateral hippocampus in MTLE are linked to the active epileptic process that seems to interfere with memory abilities.

International audience; Background. Mutations in SCN1A can cause Genetic Epilepsy with Febrile Seizures Plus (GEFS+, inherited missense mutations) or Dravet syndrome (DS, de novo mutations of all types). Although the mutational spectra are distinct, these disorders share major features and 10% of DS patients have an inherited SCN1A mutation. Objectives and patients. We studied 19 selected families with at least one DS patients to describe the mechanisms accounting for inherited SCN1A mutations in DS. The mutation identified in the DS probands was searched in available parents and relatives and quantified in the blood cells of the transmitting parent using quantitative allele-specific assays. Results. Mosaicism in the blood cells of the transmitting parent was demonstrated in 12 cases and suspected in another case. The proportion of mutated allele in the blood varied from 0.04% to 85%. In the 6 remaining families, six novel missense mutations were associated with autosomal dominant variable GEFS+ phenotypes including DS as the more severe clinical picture. Conclusion. Our results indicate that mosaicism is found in at least 7% of families with at least one DS patient and that it accounts for 68 % (13/19) of inherited mutations associated with DS. On the contrary, in the remaining cases (6/19, 32%), the patients were part of multiplex GEFS+ families and seemed to represent the extreme end of the GEFS+ clinical spectrum. In this latter case, additional genetic or environmental factors likely modulate the severity of the expression of the mutation.

Epilepsy, a neurological disorder in which patients suffer from recurring seizures, affects approximately 1% of the world population. In spite of available drug and surgical treatment options, more than 25% of individuals with epilepsy have seizures that are uncontrollable. For these patients with intractable epilepsy, the unpredictability of seizure occurrence underlies an enhanced risk of sudden unexpected death or morbidity. Therefore, a device that could predict a seizure and notify the patient of the impending event or trigger an antiepileptic device would dramatically increase the quality of life for those patients. Here, a patient-specific classification algorithm is proposed to distinguish between preictal and interictal features extracted from ECG-EEG recordings. It demonstrates that the classifier based on a Support Vector Machine (SVM) can distinguish preictal from interictal with a high degree of sensitivity and specificity. The proposed algorithm was applied to long-term recordings of 4 patients with partial epilepsy, totaling 29 seizures and more than 1333-hour-long interictal, and it produced average sensitivity and specificity values of 90.6% and 85.6% respectively using 10-minute-long window of preictal recording.

International audience; Interictal high-frequency oscillations over 200 Hz have been recorded with microelectrodes in the seizure onset zone of epileptic patients suffering from mesial temporal lobe epilepsy. Recent work suggests that similar high-frequency oscillations can be detected in the seizure onset zone using standard diagnostic macroelectrodes. However, only a few channels were examined in these studies, so little information is available on the spatial extent of high-frequency oscillations. Here, we present data on high-frequency oscillations recorded from a larger number of intracerebral contacts spatial (mean 38) in 16 patients. Data were obtained from 1 h of interictal recording sampled at 1024 Hz and was analysed using a new semi-automatic detection procedure based on a wavelet decomposition. A detailed frequency analysis permitted a rapid and reliable discrimination of high-frequency oscillations from other high-frequency events. A total of 1932 high-frequency oscillations were detected with an average frequency of 261 +/- 53 Hz, amplitude of 11.9 +/- 6.7 microV and duration of 22.7 +/- 11.6 ms. Records from a patient often showed several different high-frequency oscillation patterns. We classified 24 patterns from 11 patients. Usually (20/24 patterns) high-frequency oscillations were nested in an epileptic paroxysm, such as a spike or a sharp wave, and typically high-frequency oscillations (19/24) were recorded from just one recording contact. Unexpectedly in other cases, high-frequency oscillations (5/24) were detected simultaneously on two or three contacts, sometimes separated by large distances. This large spatial extent suggests that high-frequency oscillations may sometimes result from a neuronal synchrony manifest on a scale of centimetres. High-frequency oscillations were almost always recorded in seizure-generating structures of patients suffering from mesial (9/9) or polar (1/3) temporal lobe epilepsy. They were never found in the epileptic or healthy basal, lateral temporal or extra temporal neocortex nor in the healthy amygdalo-hippocampal complex. These findings confirm that the generation of oscillations at frequencies higher that 200 Hz is, at this scale, a specific, intrinsic property of seizure-generating networks in medial and polar temporal lobes, which have a common archaic phylogenetic origin. We show that this activity can be detected and its spatial extent determined with conventional intracranial electroencephalography electrodes in records from patients with temporal lobe epilepsy. It is a reliable marker of the seizure onset zone that should be considered in decisions on surgical treatment.